RT Journal
A1 Rafehi, Haloom
A1 Balcerczyk, Aneta
A1 Lunke, Sebastian
A1 Kaspi, Antony
A1 Ziemann, Mark
A1 KN, Harikrishnan
A1 Okabe, Jun
A1 Khurana, Ishant
A1 Ooi, Jenny
A1 Khan, Abdul Waheed
A1 Du, Xiao-Jun
A1 Chang, Lisa
A1 Haviv, Izhak
A1 Keating, Samuel T.
A1 Karagiannis, Tom C.
A1 El-Osta, Assam
T1 Vascular histone deacetylation by pharmacological HDAC inhibition
JF Genome Research 
JO Genome Research 
YR 2014 
FD August 01 
VO 24 
IS 8 
SP 1271 
OP 1284 
DO 10.1101/gr.168781.113 
UL http://genome.cshlp.org/content/24/8/1271.abstract 
AB 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.