Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.
E-GEOD-54909 - Vascular histone deacetylation by pharmacological HDAC inhibition [SAHA, ChIP-seq]
Released on 23 February 2014, last updated on 6 May 2014
HDAC inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone 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 of the mammalian genome when stimulated by the hydroxamic acids, TSA and SAHA. In primary human vascular endothelial cells we map the chromatin modifications, 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). Genome-wide mRNA sequencing indicates the differential expression of about 30% of genes, with almost equal numbers being up- and down- regulated. We observe deacetylation conferred by TSA and SAHA that are associated with decreased gene expression. Histone deacetylation is associated with the loss of p300/CBP binding at gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation. HAEC ChIP-seq profiles for 3 histone marks of SAHA treated and control samples were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Abdul W Khan, Aneta Balcerczyk, Antony Kaspi, Assam El-Osta, Haloom Rafehi, Harikrishnan Kn, Ishant Khurana, Izhak Haviv, Jenny Ooi, Jun Okabe, Lisa Chang, Mark Ziemann, Samuel T Keating, Sebastian Lunke, Tom C Karagiannis, Xiao-Jun Du