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Title: A dynamic H3K27ac signature defines VEGF-regulated endothelial enhancers      
dateReleased:
03-31-2013
description:
Histone modifications are now well-established regulators of transcriptional programs that distinguish distinct cell states. However, the kinetics of histone modification and their role in mediating rapid, signal-responsive changes in gene expression have been little studied on a genome-wide scale. Vascular endothelial growth factor A (VEGF), a major regulator of angiogenesis, rapidly triggers changes in transcriptional activity of human umbilical vein endothelial cells (HUVECs). Here we used chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) to measure genome-wide changes in histone H3 acetylation at lysine 27 (H3K27ac), a marker of active enhancers {Kharchenko et al., 2011, Nature, 471, 480-5;Zentner et al., 2011, Genome Res, 21, 1273-83;Rada-Iglesias et al., 2011, Nature, 470, 279-83; Creyghton et al., 2010, Proc Natl Acad Sci U S A, 107, 21931-6 }, after 0, 1, 4, and 12 hours of VEGF stimulation. We show that sites with greatest H3K27ac changes were associated tightly with p300, a histone acetyltransferase. This dynamic H3K27ac signature defined transcriptional elements that are functionally linked to angiogenesis, participate in rapid VEGF-stimulated changes in chromatin conformation, and mediate VEGF-induced transcriptional responses. Dynamic H3K27ac deposition required p300 activity and did not involve altered nucleosome occupancy. Our results demonstrate that capture of dynamic changes in H3K27ac provides a new approach to define the activity of functional genomic elements and implicate epigenetic modifications in rapid signal-responsive transcriptional regulation. ChiP-seq timecourse of H3K27ac, ETS1, p300 chromatin occupancy, mRNA expression and DNA hypersensitivity of HUVEC cells stimulated with VEGF for 0, 1, 4, and 12 hours
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-41166
refinement:
raw
alternateIdentifiers:
41166
keywords:
functional genomics
dateModified:
05-03-2014
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-41166/E-GEOD-41166.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-41166/E-GEOD-41166.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41166
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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