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.