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A dynamic H3K27ac signature defines VEGF-regulated endothelial enhancers[DHS]
Measurement Type: 
DNase-Hypersensitivity (DHS-Seq)
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.
Emily Merrill


A dynamic H3K27ac signature identifies VEGFA-stimulated endothelial enhancers and requires EP300 activity.
Zhang B, Day DS, Ho JW, Song L, Cao J, Christodoulou D, Seidman JG, Crawford GE, Park PJ, Pu WT
Genome Res. 2013 Jun; 23(6):917-27. PMID: 23547170. Abstract
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