The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation.

TLDR

Posttranslational modifications of histones, particularly acetylation, play a key role in gene regulation by balancing deacetylase and acetylase activity during processes such as replication, transcriptional silencing, and activation. The study aimed to investigate how histone hyperacetylation affects gene expression by using two specific histone deacetylase inhibitors, trichostatin A and trapoxin. They treated human lymphoid cell lines with TSA and TPX, confirming HDAC inhibition, and assessed gene expression changes via differential display. The inhibitors blocked HDAC activity but did not alter acetylation rates; they activated HIV‑1 transcription, reduced c‑myc expression, left GAPDH unchanged, and revealed that only about 2 % of cellular genes (8 of ~340) were affected, indicating that a limited set of genes is highly sensitive to histone acetylation levels.

Abstract

Posttranslational modifications of histones in chromatin are emerging as an important mechanism in the regulation of gene expression. Changes in histone acetylation levels occur during many nuclear processes such as replication, transcriptional silencing, and activation. Histone acetylation levels represent the result of a dynamic equilibrium between competing histone deacetylase(s) and histone acetylase(s). We have used two new specific inhibitors of histone deacetylase, trichostatin A (TSA) and trapoxin (TPX), to probe the effect of histone hyperacetylation on gene expression. We confirm that both drugs block histone deacetylase activity and have no detectable effects on histone acetylation rates in human lymphoid cell lines. Treatment with either TSA or TPX results in the transcriptional activation of HIV-1 gene expression in latently infected cell lines. In contrast, TSA and TPX cause a rapid decrease in c-myc gene expression and no change in the expression of the gene for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using differential display to compare the differences in gene expression between untreated cells and cells treated with TSA, we found that the expression of approximately 2% of cellular genes (8 genes out of approximately 340 examined) changes in response to TSA treatment. These results demonstrate that the transcriptional regulation of a restricted set of cellular genes is uniquely sensitive to the degree of histone acetylation in chromatin.