Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators
| Autor: | Assam El-Osta, Haloom Rafehi, Tom Karagiannis |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Histone Acetyltransferase p300 Histone deacetylase 5 Histone acetylation and deacetylation Binding Sites HDAC11 General Medicine Biology HDAC4 Molecular biology Histone Deacetylases Cell biology Histone Deacetylase Inhibitors Histones 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Histone methyltransferase Drug Discovery Histone H2A Humans Histone deacetylase Protein Processing Post-Translational Transcription Factors |
| Zdroj: | Current topics in medicinal chemistry. 17(14) |
| ISSN: | 1873-4294 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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