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| Status |
Public on Feb 23, 2014 |
| Title |
Vascular histone deacetylation by pharmacological HDAC inhibition [TSA, RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
HAEC mRNA profiles of TSA treated and control samples were generated by deep sequencing, in triplicate, using Illumina GAIIx.
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| Contributor(s) |
Rafehi H, Balcerczyk A, Lunke S, Kaspi A, Ziemann M, Kn H, Okabe J, Khurana I, Ooi J, Khan AW, Du X, Chang L, Haviv I, Keating ST, Karagiannis TC, El-Osta A |
| Citation(s) |
24732587, 29657262 |
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| Submission date |
Apr 18, 2012 |
| Last update date |
Jul 31, 2019 |
| Contact name |
Assam El-Osta |
| Organization name |
Baker Heart and Diabetes Institute
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| Lab |
Human Epigenetics
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| Street address |
75 Commercial Road
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| City |
Melbourne |
| ZIP/Postal code |
3004 |
| Country |
Australia |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE37378 |
Vascular histone deacetylation by pharmacological HDAC inhibition |
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| Relations |
| SRA |
SRP012295 |
| BioProject |
PRJNA159807 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE37376_HAEC_mRNA-seq_counts.txt.gz |
531.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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