Table of Contents
Overview
Definition of Epigenetics
Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in chromosomal structure, rather than changes in the DNA sequence itself. This field explores how chemical modifications to DNA and histones, proteins that package DNA, regulate gene expression without altering the underlying genetic code.[4.1] The term "epigenetics" was introduced by British embryologist Conrad Waddington in 1942 to describe the interactions between genes and their products that direct development and contribute to an organism's phenotype.[4.1] Key epigenetic mechanisms include DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. DNA methylation involves adding a methyl group to cytosine nucleotides within CpG sequences, influencing gene expression.[2.1] These modifications can be affected by various environmental factors such as diet, stress, and exposure to toxins, highlighting the dynamic nature of epigenetic regulation.[27.1] Furthermore, some epigenetic changes can be inherited across generations, a phenomenon known as epigenetic inheritance, where parental experiences can affect the gene expression of their offspring without altering the DNA sequence.[26.1] This aspect of epigenetics has significant implications for understanding familial diseases and the transmission of traits across generations.Mechanisms of Epigenetic Regulation
Epigenetic regulation involves several key mechanisms that modify gene expression without altering the underlying DNA sequence. One of the primary mechanisms is DNA methylation, where methyl groups are added to the DNA molecule, typically at cytosine bases, leading to the repression of gene transcription. This process is crucial in various biological contexts, including development and cellular differentiation, and is often disrupted in diseases such as cancer.[7.1] Histone modifications also play a significant role in epigenetic regulation. The addition or removal of chemical groups to histone proteins can alter the chromatin structure, thereby influencing gene accessibility and expression. For instance, acetylation of histones is generally associated with gene activation, while methylation can either activate or repress gene expression depending on the specific context and location of the modification.[8.1] Non-coding RNAs, particularly microRNAs (miRNAs), are another important component of epigenetic regulation. These small RNA molecules can regulate gene expression post-transcriptionally by binding to messenger RNAs (mRNAs) and preventing their translation or promoting their degradation. This mechanism adds an additional layer of control over gene expression and is implicated in various physiological and pathological processes.[15.1] Environmental factors, such as exposure to pollutants and dietary choices, can induce epigenetic modifications that impact gene expression and health outcomes. For example, exposure to endocrine-disrupting chemicals like bisphenol A (BPA) has been shown to alter DNA methylation patterns associated with neurodevelopment and hormone regulation, potentially leading to adverse health effects.[12.1] Furthermore, chronic exposure to air pollution has been linked to significant epigenetic changes that correlate with increased risks of diseases, including cancer and cardiovascular conditions.[14.1]History
Early Concepts and Definitions
The term "epigenetics" was first introduced in 1942 by embryologist Conrad Waddington, who defined it as the complex of developmental processes that occur between the genotype and phenotype, drawing from the 17th-century concept of "epigenesis".[41.1] Initially, the term referred to the poorly understood processes by which a fertilized zygote develops into a mature organism, emphasizing the developmental trajectory rather than the genetic code itself.[43.1] As scientific understanding progressed, the definition evolved to focus on heritable traits that arise not from changes in the nucleotide sequence but from chemical modifications of DNA and the proteins associated with it.[44.1] Waddington's work laid the groundwork for contemporary epigenetics by demonstrating how environmental factors could influence genetic expression and even lead to the inheritance of acquired characteristics.[80.1] His 1957 illustration of the "epigenetic landscape" depicted the differentiation of cells from an undifferentiated state to distinct cell fates, symbolizing the complex interplay between genetic and environmental influences during development.[81.1] This conceptual framework has been pivotal in shaping modern research methodologies in epigenetics, highlighting the importance of both genetic and environmental factors in the regulation of gene expression.[80.1] The increasing body of research in recent decades has underscored the significance of epigenetic modifications, such as DNA methylation and histone modifications, in regulating cell type-specific gene expression and other physiological functions.[45.1] This historical evolution of the concept of epigenetics reflects a growing recognition of the intricate mechanisms that govern gene expression beyond the genetic code itself.[42.1]Evolution of Epigenetics Terminology
The evolution of epigenetics terminology can be traced back to the early 20th century, with significant contributions from various scientists. The term "epigenetics" was first introduced by Conrad Hal Waddington in 1942, as a refinement of his earlier concept of the "epigenetic landscape" proposed in 1940. Waddington used the term to describe the interactions between environmental factors and genetic elements that lead to the development of phenotypes, emphasizing the importance of both internal and external influences on gene expression and development.[77.1] Waddington's epigenetic landscape metaphor illustrated how cells navigate through various developmental pathways, akin to balls rolling down a landscape of bifurcating valleys, where each valley represents a potential cell fate.[57.1] This model not only highlighted the role of genetic factors but also underscored the significance of environmental influences on cellular differentiation.[56.1] His ideas laid the groundwork for contemporary research methodologies in epigenetics, paving the way for a deeper understanding of gene-environment interactions.[78.1] In the decades following Waddington's introduction of the term, the field of epigenetics expanded significantly, incorporating various chemical modifications to DNA and histones that regulate gene expression. These modifications, such as methylation and acetylation, play crucial roles in chromatin structure and gene regulation, contributing to heritable traits.[83.1] The terminology and concepts surrounding epigenetics have continued to evolve, reflecting advancements in our understanding of the complex interplay between genetics and environmental factors in shaping biological outcomes.Recent Advancements
Epigenetics in Disease Research
Recent advancements in epigenetics have significantly influenced disease research, particularly in understanding the mechanisms underlying various health conditions. The term "epigenetics," first introduced by Conrad Waddington in 1942, has evolved to encompass the collective heritable changes that affect gene expression without altering the DNA sequence itself. This includes mechanisms such as DNA methylation, histone modifications, and chromatin remodeling, which play crucial roles in regulating gene activity and cellular function.[91.1] In the realm of cancer research, substantial progress has been made in targeting epigenetic mechanisms for therapeutic purposes. Over the past two decades, there has been a notable increase in drug discovery efforts aimed at developing cancer epigenetic therapeutics. These efforts have led to successful clinical developments and approvals of treatments that exploit the unique epigenetic landscapes of tumors. Key strategies include the use of small molecules that modify histone acetylation and methylation, as well as approaches based on synthetic lethality to target cancers with mutations in epigenetic regulators.[89.1] Moreover, the study of epigenetic mechanisms has expanded to include the impact of environmental factors, such as nutrition and stress, on gene expression. Research indicates that stress can directly influence DNA through epigenetic modifications, thereby affecting gene transcription and potentially leading to various health outcomes.[99.1] Nutritional epigenetics has emerged as a field that examines how bioactive food components can modify epigenetic markers, influencing gene expression and disease risk. For instance, diets rich in specific nutrients like folate, polyphenols, and omega-3 fatty acids have been shown to promote protective gene expression and mitigate harmful epigenetic changes, thereby reducing the risk of chronic diseases such as heart disease.[105.1] Additionally, novel technologies have been developed to enhance the analysis of epigenetic modifications. Techniques such as BisChIP-seq allow for a comprehensive understanding of the relationship between DNA methylation and epigenetic regulators at a genome-wide scale, facilitating significant discoveries in the field.[90.1] These advancements underscore the importance of epigenetics in disease research, highlighting its potential for personalized medicine approaches that consider individual genetic and environmental contexts.[107.1]Epigenetics-Targeted Therapies
Recent advancements in epigenetic therapies have significantly transformed the landscape of cancer treatment, focusing on the modulation of gene expression without altering the underlying DNA sequence. Key mechanisms targeted by these therapies include DNA methylation, histone modifications, and non-coding RNAs, which play essential roles in regulating gene expression and tumor behavior.[104.1] Over the past two decades, there has been a notable increase in the discovery and clinical development of drugs that target these epigenetic mechanisms, leading to the approval of several agents for clinical use.[103.1] Among the notable successes in this field are the FDA-approved DNA methyltransferase (DNMT) inhibitors, azacytidine and decitabine, which are used for treating myelodysplastic syndromes and leukemia, as well as the histone deacetylase (HDAC) inhibitor vorinostat for cutaneous T cell lymphoma.[102.1] These agents have demonstrated the ability to induce a viral mimicry state in cancer cells, which can enhance the efficacy of immune therapies when used in combination.[102.1] Current research is also exploring the potential of small-molecule inhibitors that target chromatin- and histone-modifying enzymes. These inhibitors aim to reverse epigenetic alterations in tumors and restore normal epigenetic states, leading to the upregulation of genes silenced by promoter DNA methylation.[122.1] Furthermore, the use of epigenetic therapies has shown promise in enhancing the effectiveness of traditional chemotherapy by sensitizing cancer cells and overcoming acquired resistance.[124.1] In clinical trials, various epigenetic drugs are being tested, including those that target histone lysine methylation, which represent a significant frontier in cancer treatment.[120.1] The development of these therapies is guided by a growing understanding of the epigenetic landscape of tumors, which includes alterations in DNA methylation patterns and histone modifications that can serve as biomarkers for cancer detection and classification.[122.1] Overall, the integration of epigenetic therapies into cancer treatment regimens is paving the way for more personalized and effective therapeutic strategies.In this section:
Epigenetic Mechanisms
DNA Methylation
DNA methylation is a critical epigenetic mechanism that involves the addition of a methyl group to the cytosine nucleotide within a cytosine-guanine (CpG) dinucleotide sequence. This modification is primarily catalyzed by DNA methyltransferase enzymes, which play a significant role in regulating gene expression without altering the underlying DNA sequence.[126.1] The predominant form of DNA methylation in mammals occurs at CpG sites, although evidence suggests that non-CpG methylation is also prevalent.[129.1] Methylation of cytosine bases in promoter regions is particularly important, as it has been implicated in transcriptional repression. Specifically, the presence of methylated cytosines in these regions can prevent the binding of transcription factors or attract chromatin remodeling mediators, thereby silencing gene expression.[129.1] The maintenance of DNA methylation patterns during cell division is primarily ensured by the enzyme DNMT1, while DNMT3A and DNMT3B are responsible for de novo methylation of unmethylated sites, targeting different sequences based on cell type and developmental stage.[129.1] In addition to its role in normal cellular processes, aberrations in DNA methylation patterns have been associated with various human diseases, including cancer and metabolic disorders. These changes can serve as potential biomarkers for early disease detection.[128.1] Furthermore, environmental factors such as diet, stress, and exposure to endocrine-disrupting chemicals can influence DNA methylation patterns, highlighting the dynamic nature of this epigenetic modification.[147.1] Overall, DNA methylation is a fundamental mechanism of epigenetic regulation that significantly impacts gene expression and cellular function.Histone Modification
Histone modification is a crucial aspect of epigenetic regulation, involving various post-translational modifications that influence gene expression without altering the underlying DNA sequence. These modifications include methylation, acetylation, phosphorylation, and ubiquitination of histone proteins, which play significant roles in the regulation of chromatin structure and function.[143.1] The interplay between histone modifications and DNA methylation is particularly important in establishing patterns of gene repression during development. For instance, during the reprogramming of somatic cells, pluripotency genes are reactivated through changes in histone modifications followed by the demethylation of DNA.[144.1] This interaction is essential for maintaining cellular identity and facilitating differentiation processes. Histone modifications are also implicated in the progression of various diseases, including cancer. The activation of oncogenes and the suppression of tumor suppressor genes are often associated with specific histone modifications, which can lead to the formation of cancer hallmarks.[138.1] Moreover, epigenetic alterations, such as histone modifications, can be influenced by environmental factors, including dietary components, which may further impact health outcomes.[140.1] Research has demonstrated that certain dietary phytochemicals can interact with histone modification pathways, thereby influencing gene expression and potentially altering disease risk.[141.1] For example, a diet rich in specific nutrients has been shown to promote protective gene expression while reducing harmful epigenetic modifications, highlighting the significance of nutritional epigenetics in health and disease prevention.[142.1]In this section:
Environmental Influences On Epigenetics
Impact of Lifestyle Factors
Lifestyle factors play a significant role in shaping epigenetic modifications, which can influence gene expression and overall health. Various lifestyle elements, including diet, physical activity, tobacco use, alcohol consumption, and exposure to environmental pollutants, have been identified as potential contributors to epigenetic changes.[169.1] For instance, poor nutrition and exposure to environmental toxins can disrupt brain chemistry, while chronic stress from financial hardship or unsafe living conditions may lead to long-term mental health challenges.[175.1] Research indicates that specific dietary components, such as polyphenols and flavonoids, can act as epigenetic mediators, modifying epigenetic tags and controlling gene expression.[178.1] Additionally, studies have shown that environmental exposures, such as pesticides and heavy metals, can induce significant epigenetic alterations that contribute to disease susceptibility.[177.1] Moreover, lifestyle factors can leave epigenetic marks on DNA that impact gene expression in both protective and harmful ways. For example, maternal exposure to a Western diet has been shown to alter gene expression related to physical activity in offspring.[172.1] Similarly, prenatal exposure to chemicals like BPA has been linked to changes in the epigenome that may increase the risk of neoplastic development.[172.1] The interplay between lifestyle factors and epigenetic changes underscores the potential for lifestyle modifications to reverse epigenetic alterations. Since epigenetic modifications are reversible, adopting healthier lifestyle choices, such as improved diet and moderate physical activity, may mitigate the adverse effects of environmental exposures and contribute to better health outcomes.[175.1] Understanding these connections is crucial for developing effective interventions and treatment approaches that target the underlying epigenetic changes associated with various health conditions.[173.1]Transgenerational Epigenetic Inheritance
Transgenerational epigenetic inheritance refers to the transmission of epigenetic changes across generations, which can occur as a result of environmental exposures. Research indicates that environmental pollutants can induce significant epigenetic alterations, such as changes in DNA methylation and histone modifications, which may be passed down to subsequent generations. For instance, prenatal exposure to chemicals like bisphenol A (BPA) and phthalates has been shown to influence gene expression in sperm through epigenetic mechanisms, suggesting a pathway for inter- and trans-generational inheritance of toxic chemical-induced epigenetic patterns.[191.1] Moreover, studies have demonstrated that maternal exposure to heavy metals, such as lead, can result in DNA methylation changes that are transmitted to grandchildren, highlighting the potential for long-term health implications stemming from environmental exposures.[191.1] This phenomenon underscores the importance of understanding how epigenetic modifications can reflect environmentally-induced changes and their implications for future disease risk.[194.1] In addition to chemical exposures, early-life adversities, including unpredictable sensory signals from caregivers, have been identified as significant contributors to adverse mental health outcomes. These experiences can lead to persistent alterations in neurodevelopment and mental health, further emphasizing the role of environmental factors in shaping epigenetic landscapes across generations.[188.1] The recognition of these transgenerational effects opens avenues for behavioral interventions aimed at mitigating the impact of early-life stressors and environmental pollutants, potentially reducing the burden of associated health risks.[188.1]In this section:
Epigenetics And Disease
Role in Cancer
Epigenetics plays a significant role in the development and progression of cancer through various mechanisms that regulate gene expression without altering the underlying DNA sequence. One of the primary mechanisms involves DNA methylation, where the addition of methyl groups to specific DNA regions can silence tumor suppressor genes, thereby promoting oncogenesis. For instance, hypermethylation of the p16INK4a gene has been implicated in various cancers, leading to its transcriptional silencing and contributing to uncontrolled cell proliferation.[218.1] In addition to DNA methylation, histone modifications also play a crucial role in cancer biology. These modifications can alter chromatin structure, affecting the accessibility of transcriptional machinery to DNA. For example, specific histone methylation patterns have been associated with the activation of oncogenes and the repression of tumor suppressor genes, further driving cancer development.[235.1] Moreover, aberrant histone acetylation can lead to the disruption of normal gene expression patterns, facilitating tumorigenesis.[234.1] Environmental factors, such as exposure to tobacco smoke and dietary components, can induce epigenetic changes that increase cancer susceptibility. Tobacco smoke has been shown to cause specific patterns of gene hypermethylation that serve as biomarkers for lung cancer.[218.1] Similarly, dietary factors, including caloric restriction or high-fat diets, can lead to epigenetic modifications that alter metabolic pathways and influence cancer risk.[216.1] Furthermore, epigenetic changes can also affect immune responses, which are critical in cancer progression. For instance, infections can induce epigenetic alterations in immune cells, potentially leading to a decreased ability to combat tumor cells.[209.1] This interplay between epigenetics and the immune system underscores the complexity of cancer biology and highlights the potential for epigenetic therapies as novel treatment strategies.[210.1]Implications for Public Health
Public health initiatives play a crucial role in educating communities about the impact of environmental factors on epigenetic changes. Many individuals targeted by public health messages often possess limited understanding of how social environments influence health, as well as low literacy regarding the interaction between genes and environmental factors that affect health outcomes.[181.1] This gap in knowledge highlights the need for effective public health strategies that can enhance awareness of epigenetics and its implications for health. Epigenetics is characterized by dynamic exposures that can change over short periods, necessitating careful consideration in research to avoid misinterpretations regarding the role of epigenetics in disease.[213.1] Public health initiatives can address this by promoting research that investigates the associations between epigenetic markers, socioeconomic status, and adverse health outcomes, thereby contributing to health equity.[183.1] By focusing on the interplay between environmental factors and gene expression, public health campaigns can help communities understand how lifestyle choices, such as diet and exposure to pollutants, can influence health through epigenetic modifications.[215.1] Nutritional epigenetics, a subfield of epigenetics, examines how specific nutrients and dietary patterns can affect gene expression without altering the DNA sequence. For instance, certain compounds in food can modify epigenetic markers, such as DNA methylation, which has significant implications for health and disease prevention.[219.1] Public health initiatives can leverage this knowledge by promoting diets rich in key nutrients like folate, polyphenols, and omega-3 fatty acids, which have been shown to positively influence epigenetic markers and reduce disease risk.[221.1] Moreover, the relationship between dietary patterns and epigenetic modifications is particularly relevant in addressing public health concerns such as non-alcoholic fatty liver disease (NAFLD). Emphasizing this connection can aid in the prevention and management of metabolic disorders, aligning with global health goals.[222.1] As research continues to uncover how specific dietary behaviors lead to changes in epigenetic patterns, public health strategies can be tailored to encourage healthier eating habits that promote beneficial epigenetic modifications.[223.1] In addition to dietary influences, epigenetic modifications have emerged as promising biomarkers for the early detection and prevention of chronic diseases. These modifications can serve as indicators for disease susceptibility, allowing for a shift from reactionary to preventative medicine.[228.1] Public health initiatives can utilize these biomarkers to enhance diagnostic accuracy and improve prognostic assessments, particularly in conditions such as cardiovascular diseases and cancer.[227.1] By integrating epigenetic research into public health frameworks, communities can be better equipped to understand and mitigate health risks associated with environmental and lifestyle factors.In this section:
Future Directions
Challenges in Epigenetic Research
Despite the promising potential of epigenetic therapies, several challenges hinder the effective translation of epigenetic research into clinical practice. One significant challenge is the complexity and dynamic nature of the epigenome, which can vary considerably between individuals and even within different tissues of the same individual.[252.1] This variability complicates the development of standardized treatment protocols and necessitates a deeper understanding of individual epigenetic landscapes. Moreover, the integration of epigenetic biomarkers into clinical settings faces obstacles related to the adaptation of analytical methods to the specific nature of these biomarkers. For instance, techniques such as bisulfite treatment for DNA methylation analysis or exosome isolation for circulating microRNA analysis must be tailored to the biomarker in question.[264.1] Additionally, the emergence of new biomarkers requires the implementation of advanced technologies capable of high-throughput experiments, such as next-generation sequencing (NGS) and mass spectrometry, to accurately measure epigenetic modifications.[264.1] Another critical aspect is the need for a comprehensive understanding of the social determinants of health and their interplay with epigenetic modifications. While there has been progress in investigating how external factors influence epigenetic changes, health disparities within minority populations remain inadequately addressed.[250.1] Initiatives like the NIH's funding opportunities for Social Epigenomics Research aim to bridge this gap by advancing knowledge of how social factors contribute to epigenetic changes affecting minority health.[251.1] Furthermore, the integration of epigenetic therapies with existing cancer treatments presents its own set of challenges. For example, the heterogeneity of cancer cells, driven by epigenetic modifications, complicates treatment responses and can lead to drug resistance.[253.1] Addressing these challenges requires a multifaceted approach that combines epigenetic therapies with other modalities, such as RNA-based drugs and personalized vaccines, to create more effective and durable cancer treatments.[262.1]Potential for Personalized Medicine
The integration of epigenetic biomarkers into clinical practice holds significant promise for personalizing cancer treatment and improving patient outcomes. Epigenetic changes, such as DNA methylation and histone modifications, have been identified as potential biomarkers for early cancer detection, tumor prognosis, and treatment response, although their translation into clinical practice remains limited despite advancements in the field.[257.1] The reversibility of these epigenetic modifications, unlike genetic changes, makes them attractive targets for drug development, offering new avenues for therapeutic interventions.[259.1] Recent advancements in epigenetic therapies, particularly those targeting DNA methylation, such as azacitidine, aim to reactivate silenced genes, thereby providing innovative strategies for cancer treatment.[270.1] Additionally, small-molecule inhibitors that target chromatin- and histone-modifying enzymes have shown success in clinical trials, effectively reversing epigenetic alterations in tumors and restoring normal epigenetic states.[271.1] These inhibitors not only enhance the expression of genes silenced by promoter DNA methylation but also exhibit high selectivity for cancer cells, which is crucial for personalized medicine approaches.[271.1] Moreover, the development of electrochemical biosensing technologies has emerged as a competitive method for the analysis of cancer-related epigenetic biomarkers. This approach is characterized by its user-friendly nature, multiplexing ability, simplicity, and cost-effectiveness, which are essential for clinical oncology applications.[247.1] The accurate analysis of these biomarkers at various molecular levels is anticipated to facilitate early diagnosis and improve therapeutic efficiency through personalized treatments.[247.1] The application of CRISPR-dCas9 technology represents another frontier in targeting cancer epigenetics. This technology allows for precise modifications of epigenetic changes associated with cancer, and ongoing research aims to address challenges related to delivery methods and expand its therapeutic potential.[248.1] As the field progresses, the identification and validation of epigenetic biomarkers will be crucial for enhancing treatment strategies and guiding future research directions in cancer therapy.[269.1]In this section:
References
[2] Genetics, Epigenetic Mechanism - StatPearls - NCBI Bookshelf — Introduction Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome rather than in the DNA sequence. Despite not directly altering the DNA sequence, epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure in which DNA is packaged. These epigenetic modifications can be induced by several factors including age, diet, smoking, stress, and disease state. Three different epigenetic mechanisms have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Catalyzed by DNA methyltransferase enzymes, DNA methylation involves the addition of a methyl group directly to a cytosine nucleotide within a cytosine-guanine sequence (CpG), which are often surrounded by other CpG’s forming a CpG island.
[4] Epigenetics | Definition, Inheritance, & Disease | Britannica — Epigenetics studies have revealed that chemical modifications to histones can be inherited and define how the information in genes is expressed and used by cells. Epigenetic modifications can define how the information in genes is expressed and used by cells. The term epigenetics came into general use in the early 1940s, when British embryologist Conrad Waddington used it to describe the interactions between genes and gene products, which direct development and give rise to an organism’s phenotype (observable characteristics). Since then, information revealed by epigenetics studies has revolutionized the fields of genetics and developmental biology. Specifically, researchers have uncovered a range of possible chemical modifications to deoxyribonucleic acid (DNA) and to proteins called histones that associate tightly with DNA in the nucleus.
[7] Novel Approaches to Epigenetic Therapies: From Drug Combinations to ... — Cancer cells are characterized by global epigenetic reorganization resulting in the CpG-specific hypermethylation of tumor suppressor gene promoters and global DNA hypomethylation at microsatellite regions, repetitive sequences, and oncogene promoters . The advantages of such combinations, as compared to standard chemotherapy, are the following: Epigenetic drugs can be used for priming cancer cells for chemotherapy by chemosensitization and immunopotentiation of cancer cells; epigenetic drugs can have synergistic effects with other anticancer therapies, or they can be used to reverse acquired therapy resistance. 12.Nunes S.P., Henrique R., Jerónimo C., Paramio J.M. DNA Methylation as a Therapeutic Target for Bladder Cancer. 57.Li J., Hao D., Wang L., Wang H., Wang Y., Zhao Z., Li P., Deng C., Di L.J. Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy.
[8] PDF — progression of genetic disorders, offering new opportunities for diagnosis, treatment, and prevention. By unraveling the epigenetic basis of genetic diseases, researchers are poised to usher in a new era of precision medicine, where tailored therapies based on individual epigenetic profiles hold the
[12] Air pollution-induced epigenetic changes: disease development and a ... — Several studies indicated that a DNA methylation pattern can be greatly influenced by environmental factors like ambient air pollution, and these epigenetic changes are linked with diverse diseases (Plusquin et al. Chronic exposure to air pollution causes cytogenetic damage, DNA-strand breakage, epigenetic changes, and altered gene expression—all these changes are associated with higher risk factors for many diseases, especially for cancers (Ghorani-Azam et al. Another study has shown that short-term exposure to air pollution alters DNA methylation at the promoter region of the iNOS gene (Salam et al. Expressions of many inflammatory and immune response genes are found to be altered due to DNA methylation linked with air pollution (Vawda et al.
[14] Air pollution and DNA methylation: effects of exposure in humans — Air pollution exposure is estimated to contribute to approximately seven million early deaths every year worldwide and more than 3% of disability-adjusted life years lost. Air pollution has numerous harmful effects on health and contributes to the development and morbidity of cardiovascular disease, metabolic disorders, and a number of lung pathologies, including asthma and chronic obstructive
[15] Epigenetic Regulation in Psychosomatics and Psychotherapy — Epigenetic modifications play a pivotal role in the regulation of gene expression and cell function, offering potential markers of disease states and therapeutic outcomes. Recent advancements in neuroscience have spurred interest in studying the epigenetic underpinnings of psychosomatic medicine. This review presents a new perspective on the role of epigenetic regulation in the realms of
[26] What Is Epigenetic Inheritance? » ScienceABC — Transgenerational epigenetic inheritance is the transmission of the epigenome or epigenetic markers from one generation to the next without affecting the fundamental structure of DNA. When the sperm and the egg cell meet, they transfer all their DNA into the zygote. This includes the epigenome.
[27] The Role of Epigenetics in Human Disease - News-Medical.net — Epigenetics plays a critical role in human health by regulating gene expression without the direct modification of DNA sequence. Aberrant epigenetic modifications mediated by changes in DNA and histone methylation and acetylation patterns, in addition to non-coding RNAs, can disrupt normal cellular function and lead to chronic conditions such as cancer and neurological disorders. A variety of extrinsic and intrinsic environmental factors, including nutrition, exposure to toxins, inflammation, aging, exercise, medication, social stress, and metabolic or hormonal disorders, have been linked to influence epigenetic patterns in germ cells.2 A healthy diet and regular exercise promote beneficial epigenetic changes, such as DNA demethylation and histone modifications, which can help prevent chronic diseases like cancer, diabetes, and cardiovascular disorders.12 Retrieved on December 10, 2024 from https://www.news-medical.net/health/Understanding-The-Role-of-Epigenetics-in-Human-Disease.aspx. <https://www.news-medical.net/health/Understanding-The-Role-of-Epigenetics-in-Human-Disease.aspx>. https://www.news-medical.net/health/Understanding-The-Role-of-Epigenetics-in-Human-Disease.aspx. News-Medical, viewed 10 December 2024, https://www.news-medical.net/health/Understanding-The-Role-of-Epigenetics-in-Human-Disease.aspx.
[41] Epigenetics: The origins and evolution of a fashionable topic — The term "epigenetics" was introduced in 1942 by embryologist Conrad Waddington, who, relating it to the 17th century concept of "epigenesis", defined it as the complex of developmental processes between the genotype and phenotype. ... 1 Jacques Loeb Centre for the History and Philosophy of the Life Sciences, Ben-Gurion University of the Negev
[42] From 1957 to Nowadays: A Brief History of Epigenetics — Due to the spectacular number of studies focusing on epigenetics in the last few decades, and particularly for the last few years, the availability of a chronology of epigenetics appears essential. Indeed, our review places epigenetic events and the identification of the main epigenetic writers, readers and erasers on a historic scale.
[43] A brief history of epigenetics - PubMed — The term "epigenetics" was originally used to denote the poorly understood processes by which a fertilized zygote developed into a mature, complex organism. With the understanding that all cells of an organism carry the same DNA, and with increased knowledge of mechanisms of gene expression, the def …
[44] A Brief History of Epigenetics - PMC - PubMed Central (PMC) — With the understanding that all cells of an organism carry the same DNA, and with increased knowledge of mechanisms of gene expression, the definition was changed to focus on ways in which heritable traits can be associated not with changes in nucleotide sequence, but with chemical modifications of DNA, or of the structural and regulatory proteins bound to it. X-chromosome inactivation in the mouse provided an early model of this kind of epigenetic mechanism that involved no DNA rearrangement (Ohno et al. It has been proposed that the definition of an epigenetic mechanism should include, in addition to the property of being maintained through cell division, a requirement for an initial signal, such as expression of a transcription factor, that is not needed once the new state is established (Berger et al.
[45] A brief history of epigenetics - ScienceDirect — One of the primary functions of epigenetic modifications is the regulation and maintenance of cell type-specific gene expression. X chromosome silencing is the prime example for another major function of epigenetic modifications in addition to cell type specific gene expression regulation – silencing of heterochromatin. NcRNAs, as one of the multiple mechanisms of epigenetics including DNA methylation, histone modification, ncRNAs and others, represent a family of structurally and functionally varied RNA species that play a variety of roles in essential physiological functions such as chromatin organization, mRNA splicing, and protein translation. Epigenetics refers to changes in gene expression that result without changes in the nucleotide sequence of the gene, the most common epigenetics are DNA methylation, histone modifications, alterations in nucleosome reconfiguration, and non-coding RNA expression.
[56] Conrad Waddington and the origin of epigenetics — Waddington's diagram to show how the developmental landscape relates to individual genes (bottom pegs) through networks of interactions in the organism. Since he also showed the influence of the external environment on canalisation of development, I have extended the diagram by adding the top part to represent the environmental influences.
[57] Bistability, bifurcations, and Waddington's epigenetic landscape — Waddington's epigenetic landscape is probably the most famous and most powerful metaphor in developmental biology. Cells, represented by balls, roll downhill through a landscape of bifurcating valleys. Each new valley represents a possible cell fate
[77] Waddington, Dynamic Systems, and Epigenetics - Frontiers — Waddington introduced the term epigenetics in 1942 (Waddington, 1942) as a refinement of his conception of an "epigenetic landscape" (Waddington, 1940). He used the term to describe the class of internal and external interactions between the environment and the genes leading to the development of phenotype.
[78] From epigenesis to epigenetics: the case of C. H. Waddington - Academia.edu — What controls the steepness of the walls, and thus the entire epigenetic landscape, is not just genes and their products, but gene-gene interactions and gene-environment interactions, an idea Waddington already stated in 1939 even though it was only in 1956 that a genetic landscape was visualized as underlying the epigenetic landscape.
[80] Conrad Waddington and the origin of epigenetics — Conrad Waddington and the origin of epigenetics | Journal of Experimental Biology | The Company of Biologists Denis Noble discusses Conrad Waddington's classic paper, ‘The genetic assimilation of the bithorax phenotype’, published in Evolution in 1956. In 1956, the British developmental biologist, Conrad Waddington, published a paper in the journal Evolution (Waddington, 1956) in which he succeeded in demonstrating the inheritance of a characteristic acquired in a population in response to an environmental stimulus. But Waddington was not simply showing the evolution of plasticity in general; he was showing how it could be exploited to enable a particular acquired characteristic in response to an environmental change to be inherited and be assimilated into the genome.
[81] Bistability, bifurcations, and Waddington's epigenetic landscape — In 1957, Conrad Hal Waddington published his famous drawing of the epigenetic landscape, which depicts how a cell progresses from an undifferentiated state to one of a number of discrete, distinct, differentiated cell fates during development [].The cell is represented by a ball, and it starts out in a valley at the back of the landscape ().As the ball rolls forward and downward, the valley
[83] How Does Histone Modification Affect Gene Expression? - CUSABIO — As mentioned in the article entitled "What a Powerful Artifact of DNA Compression - Histone", a histone modification is a series of post-translational modification (PTM) to histone proteins including methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation.The PTMs made to histones can impact gene expression though altering chromatin structure or recruiting histone modifiers.
[89] Epigenetics and Early Development - PMC - PubMed Central (PMC) — Once dubbed a series of chemical tags that modify DNA and its associated structures, today’s view of the epigenome during development is that of an omnipotent control entity that shapes all stages of the development of an organism through mechanisms as diverse as DNA methylation, histone modifications, remodeling via ATP-dependent chromatin complexes, histone variant exchange, Polycomb complex mediated gene silencing, chromatin dynamics, heterochromatin effects on mitotic spindle anchorage, and interactions with environmental factors from nutrition to drugs and stress. In conclusion, this review has highlighted some of the powerful effects of key epigenetic factors, including DNA methylation, histone modifications, and chromatin remodeling complexes in the control of transcription and morphogenesis during mouse and human development.
[90] Modern Epigenetics Methods in Biological Research - PMC — Except for the conventional epigenetic technologies such as bisulfite sequencing for analysis of DNA methylation status and ChIP assay for detection of chromatin modifications, a number of novel tools and techniques have been developed on the basis of traditional platforms that allow scientists to make significant discoveries . have developed a technique based on high-throughput sequencing of bisulfite-treated chromatin immunoprecipitated DNA (BisChIP-seq), which can directly interpret the relationship between DNA methylation and important epigenetic regulators at the genome-wide scale . .Kernaleguen M, Daviaud C, Shen Y, Bonnet E, Renault V, Deleuze JF, Mauger F, Tost J, Whole-Genome Bisulfite Sequencing for the Analysis of Genome-Wide DNA Methylation and Hydroxymethylation Patterns at Single-Nucleotide Resolution, Methods Mol Biol 1767 (2018) 311–349.
[91] Epigenetics-targeted drugs: current paradigms and future challenges — Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation.
[99] Epigenetic Influence of Stress and the Social Environment — The study of epigenetic mechanisms within the context of effects of social experience and stressors has provided increasing support for the hypothesis that modifications to gene expression that are observed as a consequence of these experiences may involve epigenetic pathways (Champagne 2010). In particular, variation in DNA methylation and
[102] Cancer epigenetic therapy: recent advances, challenges, and emerging ... — These agents led to the initial clinical successes of cancer epigenetic therapy, with FDA approval of DNMT inhibitors azacytidine and decitabine for the treatment of myelodysplastic syndromes (MDS) and leukemia, and HDAC inhibitor vorinostat (also known as suberoylanilide hydroxamic acid (SAHA)) for the treatment of cutaneous T cell lymphoma (CTCL). doi: 10.1016/j.cell.2017.10.022 [DOI] [PMC free article] [PubMed] [Google Scholar] doi: 10.1016/j.cell.2015.07.011 [DOI] [PMC free article] [PubMed] [Google Scholar] doi: 10.1016/j.cell.2017.06.007 [DOI] [PMC free article] [PubMed] [Google Scholar] [DOI] [PubMed] [Google Scholar]; •• This is a great review that highlights the role of DNA methylation inhibitors in inducing a viral mimicry state in cells which forms the basis for combinations of epigenetic therapy with immune therapy. doi: 10.1016/j.cell.2010.02.027 [DOI] [PMC free article] [PubMed] [Google Scholar]
[103] Cancer epigenetic therapy: recent advances, challenges, and ... - PubMed — Over the past two decades, significant strides have been made in drug discovery efforts targeting cancer epigenetic mechanisms, leading to successes in clinical development and approval of cancer epigenetic therapeutics. This article will discuss the current therapeutic rationale guiding the discovery and development of epigenetic therapeutics, key learnings from clinical experiences and new opportunities on the horizon. Keywords: Cancer epigenetics; DNA modifications; drug combination; drug discovery; histone modifications; synthetic lethality. Histone acetylation and methylation networks constitute a large component of the human epigenome and have been the focus of small molecule cancer epigenetic drug discovery in the past two decades. Synthetic lethality approach to target cancers carrying mutations in epigenetic regulators. Synthetic lethality approach to target cancers carrying mutations in epigenetic regulators.
[104] Recent advances in epigenetic anticancer therapeutics and future ... — In this process, epigenetic regulation plays an essential role in the regulation of gene expression without alteration of DNA or RNA sequence, including DNA methylation, RNA methylation, histone modifications and non-coding RNAs. Therefore, drugs developed for the above epigenetic modulation have entered clinical use or preclinical and clinical research stages, contributing to the development of antitumor drugs greatly. Recent studies suggested that m6A could modulate the proliferation, apoptosis and metastasis of cancer cell, through regulating the cancer-associated genes (He et al., 2019). M., Mo X., Khountham S., Wang J., et al. 10.1016/j.ccr.2014.01.028 [DOI] [PMC free article] [PubMed] [Google Scholar] 10.1016/j.celrep.2015.03.037 [DOI] [PMC free article] [PubMed] [Google Scholar] 10.3390/cancers13061376 [DOI] [PMC free article] [PubMed] [Google Scholar] 10.3390/cancers13112799 [DOI] [PMC free article] [PubMed] [Google Scholar] Wang W., Zhao M., Cui L., Ren Y., Zhang J., Chen J., et al.
[105] Nutritional Epigenetics: How Diet Influences Your Genes — It highlights how certain compounds in food can modify epigenetic markers, such as DNA methylation, histone modification, and non-coding RNAs, ultimately impacting health and disease risk. Nutritional epigenetics is the study of how diet and specific nutrients influence gene expression without altering the underlying DNA sequence. By influencing gene expression, nutritional epigenetics has profound implications for health and disease prevention. Studies have shown that diets high in these nutrients can reduce the risk of heart disease by promoting protective gene expression and reducing harmful epigenetic modifications. By consuming a diet rich in key nutrients like folate, polyphenols, and omega-3s, we can positively influence epigenetic markers, promoting longevity, preventing disease, and enhancing overall well-being.
[107] How Diet Can Change Your DNA - Scientific American — One theme to emerge was the epigenetic impact of diet and lifestyle on individual health. Epigenetics is the study of how different biological and environmental signals affect gene expression.
[120] JCI - Epigenetic therapies targeting histone lysine methylation ... — Epigenetic therapies that target histone lysine methylation (HKme) represent a major frontier for the treatment of cancer and other diseases. ... but valemetostat is now in clinical trials for the treatment of BCL in Europe and for NHL (ATL, BCL, ... focus on multi-target agents and compounds in clinical trials. Front Pharmacol. 2023;14:1120911
[122] Cancer epigenetics: from laboratory studies and clinical trials to ... — Many small-molecule inhibitors targeting chromatin- and histone-modifying enzymes to reverse epigenetic alterations in tumors and restore the normal epigenetic state are successful as cancer therapeutics in clinical trials (Table 1). These inhibitors lead to the preferential upregulation of genes with promoter DNA methylation and exhibit high targeting selectivity in cancer cells. Moreover, genetic and epigenetic data, (including structural variations, gene expression profiles, DNA methylation patterns, histone modification profiles, and 3D structures of the cancer genome) are key factors in personalized medicine (Fig. 2A). The altered epigenome of tumor cells (including DNA methylation, histone tail modification, nucleosome localization, and abnormal patterns of 3D chromatin organization within the nucleus) are potentially effective biomarkers to detect cancer cells and classify tumor types.
[124] Novel Approaches to Epigenetic Therapies: From Drug Combinations to ... — Cancer cells are characterized by global epigenetic reorganization resulting in the CpG-specific hypermethylation of tumor suppressor gene promoters and global DNA hypomethylation at microsatellite regions, repetitive sequences, and oncogene promoters . The advantages of such combinations, as compared to standard chemotherapy, are the following: Epigenetic drugs can be used for priming cancer cells for chemotherapy by chemosensitization and immunopotentiation of cancer cells; epigenetic drugs can have synergistic effects with other anticancer therapies, or they can be used to reverse acquired therapy resistance. 12.Nunes S.P., Henrique R., Jerónimo C., Paramio J.M. DNA Methylation as a Therapeutic Target for Bladder Cancer. 57.Li J., Hao D., Wang L., Wang H., Wang Y., Zhao Z., Li P., Deng C., Di L.J. Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy.
[126] Genetics, Epigenetic Mechanism - StatPearls - NCBI Bookshelf — Introduction Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome rather than in the DNA sequence. Despite not directly altering the DNA sequence, epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure in which DNA is packaged. These epigenetic modifications can be induced by several factors including age, diet, smoking, stress, and disease state. Three different epigenetic mechanisms have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Catalyzed by DNA methyltransferase enzymes, DNA methylation involves the addition of a methyl group directly to a cytosine nucleotide within a cytosine-guanine sequence (CpG), which are often surrounded by other CpG’s forming a CpG island.
[128] An Overview of Epigenetics - ScienceDirect — An Overview of Epigenetics - ScienceDirect Finally, a number of human diseases, such as cancer, brain disorders, and metabolic syndromes have been associated with aberrations in epigenetic processes that now open a new area of advances in epigenetic therapy. Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease Handbook of Epigenetics, 2017, pp. Handbook of Epigenetics, 2017, pp. Cookies are used by this site. Cookie settings We use cookies that are necessary to make our site work. Functional Cookies Functional Cookies These cookies may be set through our site by our advertising partners. If you do not allow these cookies, you will experience less targeted advertising.
[129] Epigenetics: Definition, Mechanisms and Clinical Perspective — Although covalent modifications of DNA bases have been described since 1948,7 it was only in 1969 that Griffith and Mahler suggested that these modifications may modulate gene expression.8 The predominant modification in mammalian DNA is methylation of cytosine,7 followed by adenine and guanine methylation.7,9 Although methylation of cytosine bases in mammalian DNA has been primarily described in the context of CpG dinucleotides,10 evidence suggests that cytosines in non-CpG sequences are also frequently methylated.11–13 Because the promoter regions of silenced genes possess significantly more methylated cytosines in comparison with actively transcribed genes, this modification has been implicated in transcriptional repression.14,15 Methylation of cytosine in the promoter region may repress gene expression by preventing the binding of specific transcription factors16 or may attract mediators of chromatin remodeling, such as histone-modifying enzymes or other repressors of gene expression.17–20 In mammals, the mitotic inheritance of methylated DNA bases is primarily ensured by a maintenance of DNA methyltransferase (DNMT1),21–23 whereas DNA methylation enzymes DNMT3A and DNMT3B are mainly responsible for de novo methylation of unmethylated sites.24 Various studies have shown that DNMT3A and DNMT3B target different sites for methylation depending on the cell type and the stage of development.6,25,26 De novo methyltransferases may be directly targeted to specific DNA sequences, may necessitate the interaction with other DNA binding proteins or may be guided by RNA interference (RNAi) in a process called RNA-directed DNA methylation (RdDM).27
[138] Epigenetic regulation in human cancer: the potential role of epi-drug ... — The heritable changes, either occurring or maintaining during multiple cellular biological processes with the same genetic information, require fine-tuned epigenetic modifications, which commonly including DNA methylation, histone, or chromatin post-translational modifications (PTM), as well as non-coding RNAs regulations. The epigenetic modifications can be generally categorized into three groups: DNA and RNA methylations, histone modifications, and non-coding RNAs, which are considered as main mechanisms of regulation during carcinogenesis/cancer progression. The activation of oncogenes and/or suppression of tumour suppressor genes (TSGs) are considered to be one of factors contributed to the onset of cancer, and they are always consistent with epigenetic changes. Within tumour cells, the activated epigenetic modifiers switch on the transcription of oncogenes and onco-miRNAs, assisting the formation of cancer hallmarks.
[140] Dietary Phytochemicals in Health and Disease: Mechanisms, Clinical ... — Research shows that dietary phytochemicals interact with nuclear and membrane receptors, influence metabolic pathways, and affect epigenetic modifications. Our review highlights the broad range of biological activities of these compounds, including antioxidant, antibacterial, anti‐inflammatory, anti‐diabetic, and anticancer effects, all of
[141] Nutritional Epigenetics: How Diet Influences Your Genes — It highlights how certain compounds in food can modify epigenetic markers, such as DNA methylation, histone modification, and non-coding RNAs, ultimately impacting health and disease risk. Nutritional epigenetics is the study of how diet and specific nutrients influence gene expression without altering the underlying DNA sequence. By influencing gene expression, nutritional epigenetics has profound implications for health and disease prevention. Studies have shown that diets high in these nutrients can reduce the risk of heart disease by promoting protective gene expression and reducing harmful epigenetic modifications. By consuming a diet rich in key nutrients like folate, polyphenols, and omega-3s, we can positively influence epigenetic markers, promoting longevity, preventing disease, and enhancing overall well-being.
[142] Epigenetics and Diet: How Food Influences Gene Expression - Rupa Health — Through testing such as the DNA Diet panel by DNA Life and the Methylation Profile by Doctor’s Data, individuals can gain insight into the best way to personalize their nutrition to support favorable epigenetic activity and be proactive about their health. Additionally, including a variety of bioactive foods that have been well-studied for their potential impact on epigenetic health can also be a helpful way to support epigenetics through diet. Making simple diet and lifestyle changes can help support optimal epigenetic health and increase the potential to positively influence gene expression to reduce chronic disease risk. Following a Mediterranean-type diet that emphasizes foods linked to positive epigenetic changes, such as cruciferous vegetables, berries, grapes, garlic, turmeric, and green tea, is a simple way to support optimal health and longevity.
[143] Mechanisms of DNA methylation and histone modifications — The regulation of gene expression has been dependent on the methylation of DNA, post-translational modifications of histones, effector proteins, chromatin remodeler enzymes that affect the chromatin structure and function, and other cellular activities such as DNA replication, DNA repair, proliferation and growth. The three major categories of epigenetic regulation are histone modifications, DNA methylation, and chromatin remodeling. Of these four bases, naturally occurring methylated bases are adenine and cytosine.1, 2 This epigenetic mark, 5-methylcytosine was discovered in the living organismin around mid-1920s_, way before the discovery of DNA structure by Watson and Crick.3 DNA methylation is the epigenetic progression of regulating the expression of gene by adding methyl group to the DNA sequence with the help specific enzymes namely, DNA methyltransferases.
[144] Linking DNA methylation and histone modification: patterns and ... — Linking DNA methylation and histone modification: patterns and paradigms | Nature Reviews Genetics During reprogramming of somatic cells, pluripotency genes become reactivated in a process that involves changes in histone modification followed by demethylation of the DNA. Both DNA methylation and histone modification are involved in establishing patterns of gene repression during development. U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. E. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. References 49 and 50 show that G9a promotes DNA methylation of retrotransposons and a number of genes in embryonic stem cells independently of its catalytic activity. Polycomb mediated histone H3(K27) methylation pre-marks genes for de novo methylation in cancer. MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells.
[147] Epigenetic Modifications due to Environment, Ageing, Nutrition, and ... — Sex-steroid hormones establish methylation status during critical developmental periods , and epigenetic modifications begin as early as germ cell development and embryogenesis . EDCs can act on sex-steroid hormone receptors, so during critical developmental periods if the fetus is exposed to EDCs, remethylation could occur within the germ
[169] Epigenetics explained: How the environment alters the fate of our DNA — So far, several lifestyle factors have been identified as candidates for causing epigenetic changes including diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants, psychological stress, and working night shifts. But epigenetic signatures can also be left by traumatic events.
[172] The Impact of Nutrition and Environmental Epigenetics on Human Health ... — Lifestyle factors and environmental exposures leave epigenetic marks on our DNA that impact gene expression; some have protective effects while others are harmful. 44.Ruegsegger G.N., Grigsby K.B., Kelty T.J., Zidon T.M., Childs T.E., Vieira-Potter V.J., Klinkebiel D.L., Matheny M., Scarpace P.J., Booth F.W. Maternal Western diet age-specifically alters female offspring voluntary physical activity and dopamine-and leptin-related gene expression. 88.Dhimolea E., Wadia P.R., Murray T.J., Settles M.L., Treitman J.D., Sonnenschein C., Shioda T., Soto A.M. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development. 89.Kim J.Y., Yi B.R., Go R.E., Hwang K.A., Nam K.H., Choi K.C. Methoxychlor and triclosan stimulates ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an estrogen receptor-dependent pathway.
[173] The Role of Epigenetics in Mental Health: A Comprehensive Guide — This article will provide a comprehensive guide to the role of epigenetics in mental health, exploring the connection between epigenetic changes and specific mental health disorders, the influence of environmental factors, and the potential for new treatment approaches based on epigenetic research. Understanding the role of stress and trauma in epigenetic changes is crucial for developing effective interventions and treatments for mental health disorders. Understanding the environmental influences on epigenetic changes is crucial for developing effective interventions and treatment approaches for mental health disorders. By targeting the underlying epigenetic changes associated with mental health disorders, researchers hope to develop more effective and personalized treatments that can improve outcomes for individuals suffering from these conditions.
[175] Mental Illness Is Not in Your Genes: The Truth About Epigenetics and ... — Poor nutrition and exposure to environmental toxins can also disrupt brain chemistry, while chronic stress from financial hardship or unsafe living conditions can lead to long-term mental health challenges. Unlike fixed genetic traits, epigenetic modifications are reversible, meaning that lifestyle changes, therapy, and a supportive environment
[177] Timing of dietary effects on the epigenome and their potential ... — These epigenetic alterations underline the potential of pesticides to induce long-lasting changes in gene expression and increase disease susceptibility. Furthermore, heavy metals, including arsenic, cadmium, nickel, and chromium, induce significant epigenetic alterations that contribute to their carcinogenic effects.
[178] Epigenetic modifications of gene expression by lifestyle and ... — Epigenetic modifications of gene expression by lifestyle and environment - PubMed Search: Search Since epigenetic changes are reversible and nutrition is one of the many epigenetic regulators that modify gene expression without changing the DNA sequence, dietary nutrients and bioactive food components contribute to epigenetic phenomena either by directly suppressing DNA methylation or histone catalyzing enzymes or by changing the availability of substrates required for enzymatic reactions. We discuss the epigenetic contributions of dietary components with a particular focus on nutritional polyphenols and flavonoids as epigenetic mediators that modify epigenetic tags and control gene expression. These mechanisms provide new insights to better understand the influence of dietary nutrients on epigenetic modifications and gene expression. Link A, et al. doi: 10.1016/j.gene.2015.02.045.
[181] Imagining roles for epigenetics in health promotion research — Thus many of those targeted by public health messages have limited imaginations for the role of social environment on health (Robert & Booske, 2011), and generally low literacy regarding how genes and environment interact to influence health outcomes (Condit & Shen, 2011). An example relevant to epigenetics is that some genetic susceptibility
[183] Epigenetics: An Emerging Tool for Health Equity Science — A recent review provides recommendations to improve the scientific investigation of the associations between epigenetic markers, socioeconomic status, and adverse health outcomes.. Health equity means that everyone has the opportunity to be as healthy as possible. Health equity science studies the association between social determinants of health and adverse health outcomes.
[188] The evolving neurobiology of early-life stress - ScienceDirect — Over the past decade, a novel concept of an additional ACE, characterized by unpredictable sensory signals from the parents/caregivers and the environment, has emerged36,42,65,66 and is widely recognized.67,68,69,70,71 The importance of unpredictability of sensory inputs was initially supported by preclinical work (Figure 2; Box 3) and complementary computational models.72,73 Studies in infants have now established that unpredictable environmental signals, measured as entropy or via appropriate questionnaires (Box 3), contribute significantly to adverse neurodevelopmental outcomes in children and adolescents36,37,38,65,74 and to adult anhedonia and posttraumatic stress disorder (PTSD).75,76,77 The contribution of unpredictable experiences as an early-life stressor to mental health outcomes persists even after accounting for the predictive capacity of established ACEs.36,37,38 The relative contribution of unpredictability to the overall burden of ACEs remains unknown and likely varies in different populations depending on the dominance of other ACEs. An ongoing population study of ∼30,000 children suggests that unpredictable early-life experiences are an independent and significant risk factor, increasing the probability of depression ∼12-fold, even in the absence of other significant ACEs.78 This discovery is important because unpredictability of childhood experiences is amenable to behavioral interventions, with a potential for reducing the burden of early-life stress.14,37,38,65,78
[191] Environmental exposures influence multigenerational epigenetic ... — DNA methylation and histone modifications both influence 3D genome organization, highlighting its importance in epigenetic gene regulation . These exposures induce changes in the epigenetic landscape of an individual, shown in the inner yellow circle, through DNA methylation, histone modifications, miRNA gene regulation, and 3D genome reorganization, that can be transmitted across one or more generations. Animal models also suggest that prenatal BPA and phthalate exposures influence transcription factor expression in sperm, mediated through DNA methylation and histone modifications , suggesting a mechanism for inter- and trans-generational inheritance of toxic chemical-induced epigenetic patterns. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren.
[194] Effects of airborne pollutants on mitochondrial DNA Methylation — Epigenetic research on environmental exposures - such as airborne pollutants - that induce oxidative-stress in humans has consistently shown DNA methylation alterations in peripheral blood nuclear DNA [1, 3 - 6]. DNA methylation has thus been proposed to reflect environmentally-induced epigenomic reprogramming and risk of future disease [7
[209] Epigenetics, Health, and Disease | Genomics and Your Health | CDC — Epigenetics, Health, and Disease | Genomics and Your Health | CDC Epigenetics refers to how your behaviors and environment can cause changes that affect the way your genes work. While changes to the genes (mutations) can change the protein that is made, epigenetic changes affect gene expression to turn genes "on" and "off." This can mean that genes make proteins in cells and tissues where or when they normally would not, or that genes don't make proteins where and when they normally would. In addition, some epigenetic changes can make you more likely to develop certain diseases, such as cancer. Infections with these germs can cause epigenetic changes in some of your immune cells that result in turning off the IL-12B gene.
[210] How epigenetics impacts on human diseases - ScienceDirect — How epigenetics impacts on human diseases - ScienceDirect How epigenetics impacts on human diseases The article provides a synthetic and historical view of the origin of epigenetics and highlights some of the most relevant achievements in the field. Epigenetics is a rapidly growing field of biology that studies the changes in gene expression that are not due to alterations in the DNA sequence but rather the chemical modifications of DNA and its associated proteins. Therefore, rigorous studies are essential to minimize the risks associated with epigenetic therapies and to develop safe and effective interventions for improving human health. This article provides a synthetic and historical view of the origin of epigenetics and some of the most relevant achievements. For all open access content, the relevant licensing terms apply.
[213] Epigenetic Epidemiology: Promises for Public Health Research — Epigenetics, in contrast, are a dynamic exposure that can vary over short intervals. If samples are collected at disease diagnosis, we cannot make assumptions about the role of epigenetics as a driver of disease or a late-stage passenger of the condition. Studies must be very cautious of reverse causation in epigenetic research.
[215] Epigenetics: Environmental Impacts on Gene Expression — Epigenetics: Environmental Impacts on Gene Expression - BiologyInsights Epigenetics: Environmental Impacts on Gene Expression Explore how environmental factors influence gene expression through epigenetic modifications, shaping health and development. Epigenetics represents a fascinating dimension of biology, where gene expression is influenced by factors beyond the DNA sequence itself. These modifications shape how genes are expressed without altering the underlying genetic code. Epigenetic modifications are biochemical processes that regulate gene activity without altering the DNA sequence. Various environmental factors such as diet, pollutants, and stressors can modulate epigenetic marks, leading to alterations in gene expression patterns. This interplay between genetic and epigenetic mechanisms ensures that gene expression is precisely controlled, enabling organisms to adapt to new challenges.
[216] Epigenetic biomarkers for disease susceptibility and preventative ... — Caloric restriction or high-fat diets in mammals and humans have been shown to alter the metabolic status and disease (e.g., obesity) of the individual through epigenetic change. 21, 22 Cold or heat exposure can impact a variety of physiological processes from metabolism to reproduction through epigenetic processes. 23 Stress or trauma can
[218] Environmental Epigenetics and Its Implication on Disease Risk and ... — Epigenetic patterns from tobacco smoke have been associated with specific patterns of gene hypermethylation; these have been seen in animal models of lung cancer that could serve as biomarkers for the disease (Mathers et al. Many epigenetic alterations have been identified in hepatitis B virus X protein–induced carcinogenesis, including DNA hypermethylation of p16[INK4a] and subsequent transcriptional activation of DNMT1 in HepG2 cells through the p16(INK4a)-cyclin D1-cyclin–dependent kinase (CDK) 4/6-retinoblastoma protein (pRb)-E2F1 pathway (Jung et al. Many studies have focused on the epigenetic changes in PM or diesel exhaust particle exposure, including changes at repeat elements and specific gene promoter regions, which thus alter expression levels (Baccarelli and Bollati et al.
[219] Nutritional Epigenetics: How Diet Influences Your Genes — It highlights how certain compounds in food can modify epigenetic markers, such as DNA methylation, histone modification, and non-coding RNAs, ultimately impacting health and disease risk. Nutritional epigenetics is the study of how diet and specific nutrients influence gene expression without altering the underlying DNA sequence. By influencing gene expression, nutritional epigenetics has profound implications for health and disease prevention. Studies have shown that diets high in these nutrients can reduce the risk of heart disease by promoting protective gene expression and reducing harmful epigenetic modifications. By consuming a diet rich in key nutrients like folate, polyphenols, and omega-3s, we can positively influence epigenetic markers, promoting longevity, preventing disease, and enhancing overall well-being.
[221] Nutrition & the Epigenome - University of Utah — Epigenetics; Nutrition & the Epigenome; Nutrition & the Epigenome. Unlike behavior or stress, diet is one of the more easily studied, and therefore better understood, environmental factors in epigenetic change. ... Familiar nutrients like folic acid, B vitamins, and SAM-e (S-Adenosyl methionine, a popular over-the-counter supplement) are key
[222] Dietary Pattern's Role in Hepatic Epigenetic and Dietary ... — NAFLD has emerged as a significant public health concern, with its prevalence increasing globally. Emphasizing the complex relationship between dietary patterns and epigenetic modifications such as DNA methylation or miRNA expression can exert a positive impact on preventing and managing metabolic disorders, including NAFLD, within the 2030 Sustainable Development Goals.
[223] Editorial: Dietary Factors, Epigenetics and Their Implications for ... — Among factors involved in epigenetic modifications, the role of nutrients on DNA methylation and accessibility have gathered increasing attention because methyl group donors and related molecules contributing to DNA methylation are derived from food. ... specific dietary behaviors lead to changes in epigenetic patterns and regulate gene
[227] Epigenetic Biomarkers: New Findings, Perspectives, and Future ... — Currently, it is clear that the accurate analysis of emerging cancer epigenetic and metastatic-related biomarkers at different molecular levels is envisaged as an exceptional solution for early and reliable diagnosis and the improvement of therapy efficiency through personalized treatments. Within this field, electrochemical biosensing has demonstrated to be competitive over other emerging and currently used methodologies for the determination of these biomarkers accomplishing the premises of user-friendly, multiplexing ability, simplicity, reduced costs and decentralized analysis, demanded by clinical oncology, thus priming electrochemical biosensors to spark a diagnostic revolution for cancer prediction and eradication. The main challenges to which further work must be addressed and the impact of these advances should have in the clinical acceptance of these emerging biomarkers are also discussed which decisively will contribute to understand the molecular basis involved in the epigenetics and metastasis of cancer and to apply more efficient personalized therapies.
[228] Epigenetic biomarkers for disease susceptibility and preventative ... — This review is focused on the epigenetic biomarkers for disease susceptibility, which are distinct from epigenetics of disease etiology or progression. The development of efficient epigenetic biomarkers for disease susceptibility, before the development of pathology, will facilitate a paradigm shift from reactionary medicine to preventative medicine.
[234] Mechanisms of DNA methylation and histone modifications — The regulation of gene expression has been dependent on the methylation of DNA, post-translational modifications of histones, effector proteins, chromatin remodeler enzymes that affect the chromatin structure and function, and other cellular activities such as DNA replication, DNA repair, proliferation and growth. The three major categories of epigenetic regulation are histone modifications, DNA methylation, and chromatin remodeling. Of these four bases, naturally occurring methylated bases are adenine and cytosine.1, 2 This epigenetic mark, 5-methylcytosine was discovered in the living organismin around mid-1920s_, way before the discovery of DNA structure by Watson and Crick.3 DNA methylation is the epigenetic progression of regulating the expression of gene by adding methyl group to the DNA sequence with the help specific enzymes namely, DNA methyltransferases.
[235] Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular ... — Rather, epigenetic modifications, or “tags,” such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. This sequence of events illustrates how DNA methylation and certain histone modifications function together to contribute to the transcriptional on or off state of genes subject to epigenetic modification (Figure 1). Recent findings in mammalian cells suggest that synthetic siRNAs and endogenous miRNAs that target gene promoters may direct transcriptional gene silencing by recruiting specific argonaute proteins and forming epigenetic remodeling complexes that suppress gene expression by fostering histone deacetylation, histone methylation (H3K9 and H3K27), and DNA methylation 63–65.
[247] Epigenetic Biomarkers: New Findings, Perspectives, and Future ... — Currently, it is clear that the accurate analysis of emerging cancer epigenetic and metastatic-related biomarkers at different molecular levels is envisaged as an exceptional solution for early and reliable diagnosis and the improvement of therapy efficiency through personalized treatments. Within this field, electrochemical biosensing has demonstrated to be competitive over other emerging and currently used methodologies for the determination of these biomarkers accomplishing the premises of user-friendly, multiplexing ability, simplicity, reduced costs and decentralized analysis, demanded by clinical oncology, thus priming electrochemical biosensors to spark a diagnostic revolution for cancer prediction and eradication. The main challenges to which further work must be addressed and the impact of these advances should have in the clinical acceptance of these emerging biomarkers are also discussed which decisively will contribute to understand the molecular basis involved in the epigenetics and metastasis of cancer and to apply more efficient personalized therapies.
[248] Advances in targeting cancer epigenetics using CRISPR-dCas9 ... - PubMed — Advances in targeting cancer epigenetics using CRISPR-dCas9 technology: A comprehensive review and future prospects - PubMed Advances in targeting cancer epigenetics using CRISPR-dCas9 technology: A comprehensive review and future prospects Advances in targeting cancer epigenetics using CRISPR-dCas9 technology: A comprehensive review and future prospects The purpose of this review article is to provide a thorough analysis of recent advancements in utilizing CRISPR-dCas9 technology to target and modify epigenetic changes associated with cancer. This review aims to summarize the latest research developments, evaluate the effectiveness and limitations of CRISPR-dCas9 applications in cancer therapy, identify key challenges such as delivery methods and explore future directions for improving and expanding these technologies. Keywords: CRISPR-dCas9; Cancer epigenetics; Cancer therapy; Epigenome editing.
[250] Frontiers | Understanding the Interplay Between Health Disparities and ... — Several health disparities studies have been published using genetic-based approaches; however, increasing accessibility and affordability of molecular technologies have allowed for an in-depth investigation of the influence of external factors on epigenetic modifications (e.g., DNA methylation, micro-RNA expression). This area of research is important when it comes to understanding the biological effects of environmental (e.g., food availability, pollution, green space, etc.) or social stressors (e.g., abuse, socioeconomic stress, etc.) and how they contribute to the rising health disparities commonly affecting minority communities; however, health disparities within minority populations have not been well addressed using epigenetic approaches. The areas reviewed here are: (1) key social determinants of health, (2) common epigenetic mechanisms that affect human biology, (3) intersection of social determinants and epigenetics over the human life span, and (4) challenges and current limitations of social epigenomic studies.
[251] Advancing Health Disparities Science Through Social Epigenomics ... — In 2016, the NIH, led by NIMHD, developed funding opportunities to support Social Epigenomics Research Focused on Minority Health and Health Disparities. 8-10 The overarching objectives of this initiative were to advance understanding of mechanisms by which social factors lead to epigenetic changes that affect minority health and/or health
[252] The Role of Epigenetics in Clinical Research — Challenges in Translating Epigenetic Research to Clinical Practice Despite the promise of epigenetic therapies, several challenges remain in translating epigenetic research into clinical practice. One major challenge is the complexity and dynamic nature of the epigenome, which can vary significantly between individuals and even within different
[253] Epigenetic modifications: Key players in cancer heterogeneity and drug ... — Keywords: Epigenetic modifications, Cancer heterogeneity, Drug resistance, DNA methylation, Histone modifications, Chromatin remodeling, Epigenetic therapies, Gene expression regulation Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling, have been recognized as significant contributors to cancer heterogeneity and drug resistance . Cancer patients’ genomic-wide aberrant and variable histone modifications lead to heterogeneity of chromatin accessibility in different tumor subpopulations, which in turn causes heterogeneity in the expression of genes involved in cell proliferation, differentiation, and survival causing TME heterogeneity . Epigenetic modifications are pivotal in mediating drug resistance in cancer cells by inducing changes in gene expression profiles without alterations in the DNA sequence (Table 1).
[257] Molecular basis of epigenetic regulation in cancer diagnosis and treatment — Epigenetic changes like DNA methylation and histone modification detected in early tumorigenesis and cancer progression have been proposed as biomarkers for early cancer detection, tumor prognosis, and treatment response . They are rarely translated into biomarkers for clinical practice, even though there have been major advances in the
[259] Cancer epigenetics in clinical practice - PubMed — These cancer-specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development.
[262] Epigenetic therapies in cancer treatment: Opportunities and challenges ... — By integrating epigenetic therapies with RNA-based drugs, nanomedicine, personalized vaccines, 3D epigenomics, and artificial intelligence, this review underscores the transformative potential of these therapies in redefining oncology, offering personalized, durable, and precise solutions to the complexities of cancer.
[264] Epigenetic biomarkers: Current strategies and future challenges for ... — In addition, although new biomarkers are appearing, in the particular case of epigenetic markers there is a necessity to adapt the methods of analysis to the nature of the biomarker (i.e. bisulfite treatment for DNA methylation analysis, or exosome isolation/separation for circulating miRNA analysis) or to the new technologies able to perform high-throughput experiments (i.e. microarrays and next generation sequencing (NGS) to measure DNA methylation or microRNAs, HPLC coupled to mass spectrometry to detect PTMs in histones, etc.).
[269] Epigenetic reprogramming in cancer: From diagnosis to treatment — . 2023 Feb 14;11:1116805. doi: 10.3389/fcell.2023.1116805. Search in PMC; ... DNA methylation is an important epigenetic marker for cancer diagnosis, with direct implications for survival rate and an emergent target for drug development. ... cell therapy has revolutionized personalized cancer treatment. Some of the strategies available for this
[270] The pharmacoepigenetic paradigm in cancer treatment — Epigenetic therapies, particularly those targeting DNA methylation like azacitidine, aim to reactivate silenced genes, offering new strategies for cancer treatment. These drugs modify the epigenetic landscape, potentially reversing the gene silencing that contributes to cancer development ( Issa and Kantarjian, 2009 ; Gailhouste et al., 2018 ).
[271] Cancer epigenetics: from laboratory studies and clinical trials to ... — Many small-molecule inhibitors targeting chromatin- and histone-modifying enzymes to reverse epigenetic alterations in tumors and restore the normal epigenetic state are successful as cancer therapeutics in clinical trials (Table 1). These inhibitors lead to the preferential upregulation of genes with promoter DNA methylation and exhibit high targeting selectivity in cancer cells. Moreover, genetic and epigenetic data, (including structural variations, gene expression profiles, DNA methylation patterns, histone modification profiles, and 3D structures of the cancer genome) are key factors in personalized medicine (Fig. 2A). The altered epigenome of tumor cells (including DNA methylation, histone tail modification, nucleosome localization, and abnormal patterns of 3D chromatin organization within the nucleus) are potentially effective biomarkers to detect cancer cells and classify tumor types.