Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators.
BACKGROUND
Histone deacetylase (HDAC) enzymes control the acetylation status of transcription factors that regulate chromatin structure and gene function. The transcriptional regulatory factors that distinguish histone acetylation and deacetylation patterns by pharmacological HDAC inhibition (HDACi) have not yet been studied.


METHODS
We analysed sequencing datasets derived from human aortic endothelial cells (HAECs) stimulated with the HDAC inhibitors, Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). We integrated gene expression and histone acetylation profiles with the transcription factor binding site (TFBS) database derived from the Encyclopedia of DNA Elements (ENCODE) project.


RESULTS
Overall, TFBS signatures observed in SAHA and TSA stimulated cells were analogous. Histone acetylation was observed at transcription factor binding sites of target genes associated with the silencing factors NRSF, EZH2 and SUZ12. Histone deacetylation was a prominent property of HDACi and correlated with changes in the expression of genes regulated by proteins in transcriptional control such as histone acetyltransferase P300 and lysine demethylase JARID1A, as well as the regulatory factors cMYC, YY1 and STAT family proteins.


CONCLUSIONS
We identified several transcription factors and coregulators implicated in the regulation of histone modification at target genes mediated by pharmacological HDAC inhibition.
Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
Haloom
H
Rafehi
Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
Tom C
TC
Karagiannis
Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.
Assam
A
El-Osta
D001665:Binding Sites / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D014157:Transcription Factors; D006655:Histone Deacetylases
Deacetylation; Epigenetics; Histone Acetylation; Suberoylanilide Hydroxamic acid; Transcription factor; Trichostatin
A.