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A dynamic H3K27ac signature defines VEGF-regulated endothelial enhancers

ABSTRACT: 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

ORGANISM(S): Homo Sapiens

SUBMITTER: Lingyun Song   Gregory E Crawford  Daniel S Day  Peter J Park  William T Pu  Jingjing Cao  Joshua Ho  Bing Zhang 

PROVIDER: E-GEOD-41166 | ArrayExpress | 2013-03-31



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