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Series GSE41166 Query DataSets for GSE41166
Status Public on Mar 31, 2013
Title A dynamic H3K27ac signature defines VEGF-regulated endothelial enhancers
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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.
Overall design 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
Contributor(s) Zhang B, Day DS, Ho J, Song L, Cao J, Crawford GE, Park PJ, Pu WT
Citation(s) 23547170
Submission date Sep 26, 2012
Last update date May 15, 2019
Contact name Peter J Park
Phone 617-432-7373
Organization name Harvard Medical School
Department Center for Biomedical Informatics
Street address 10 Shattuck St
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (32)
GSM1009623 H3K27ac Hour 0
GSM1009624 H3K27ac Hour 1
GSM1009625 H3K27ac Hour 4
BioProject PRJNA176027
SRA SRP015904

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Supplementary file Size Download File type/resource
GSE41166_RAW.tar 11.0 Gb (http)(custom) TAR (of BED)
GSE41166_adaptor.txt.gz 86 b (ftp)(http) TXT
GSE41166_fpkm.csv.gz 574.1 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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