Human body epigenome maps reveal noncanonical DNA methylation variation

TLDR

Understanding the diversity of human tissues requires linking identical genetic information with tissue‑specific epigenetic mechanisms, and surveys of DNA methylation have revealed a complex landscape of tissue‑specific and invariant patterns. The study aims to catalogue cytosine methylation in all contexts across major human organ systems, integrating matched transcriptomes and genomic sequence. High‑coverage methylomes were generated for all major organ systems and combined with matched transcriptomes and genomic sequence. The integrated data revealed widespread tissue‑specific differential CG methylation, partially methylated domains, allele‑specific methylation and transcription, pervasive non‑CG methylation that correlates with tissue‑specific functions and predicts genes escaping X‑chromosome inactivation, and overall substantial variation of DNA methylation among tissues.

Abstract

Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual's cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals' phased genome, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.