Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators

Title:Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators

Volume: 17 Issue: 14

Author(s): Haloom Rafehi, Tom C. Karagiannis and Assam El-Osta*

Affiliation:

• Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC,Australia

Keywords: Epigenetics, Deacetylation, Histone Acetylation, Transcription factor, Suberoylanilide Hydroxamic acid, Trichostatin A.

Abstract: Introduction: 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.

Conclusion: We identified several transcription factors and coregulators implicated in the regulation of histone modification at target genes mediated by pharmacological HDAC inhibition.

Cite this article as:

Rafehi Haloom, Karagiannis C. Tom and El-Osta Assam*, Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators, Current Topics in Medicinal Chemistry 2017; 17 (14) . https://dx.doi.org/10.2174/1568026617666161104104341

DOI https://dx.doi.org/10.2174/1568026617666161104104341	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294