Vascular histone deacetylation by pharmacological HDAC inhibition

Haloom Rafehi, Aneta Balcerczyk, Sebastian Lunke, Anthony Kaspi, Mark Ziemann, Kaipananickal N Harikrishnan, Jun Okabe, Ishant Khurana, Jenny Ooi, Abdul Waheed Khan, Xiao-Jun Du, Lisa Hsiu Chuan Chang, Izhak Haviv, Samuel T Keating, Tom Karagiannis, Assam El-Osta

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48 Citations (Scopus)

Abstract

HDAC inhibitors can regulate gene expression by post-translational modification of histone as well as nonhistone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action. However, little is known of the extent of genome-wide changes in cells stimulated by the hydroxamic acids, TSA and SAHA. In this article, we map vascular chromatin modifications including histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation-mediated gene expression is often associated with modification of other lysine residues, we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). RNA sequencing indicates the differential expression of 30 of genes, with almost equal numbers being up- and down-regulated. We observed broad deacetylation and gene expression changes conferred by TSA and SAHA mediated by the loss of EP300/CREBBP binding at multiple gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation by pharmacological HDAC inhibition
Original languageEnglish
Pages (from-to)1271-1284
Number of pages14
JournalGenome Research
Volume24
Issue number8
DOIs
Publication statusPublished - 2014

Cite this

Rafehi, H., Balcerczyk, A., Lunke, S., Kaspi, A., Ziemann, M., Harikrishnan, K. N., Okabe, J., Khurana, I., Ooi, J., Khan, A. W., Du, X-J., Chang, L. H. C., Haviv, I., Keating, S. T., Karagiannis, T., & El-Osta, A. (2014). Vascular histone deacetylation by pharmacological HDAC inhibition. Genome Research, 24(8), 1271-1284. https://doi.org/10.1101/gr.168781.113