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Series GSE93030 Query DataSets for GSE93030
Status Public on Dec 31, 2016
Title VEGF promotes RNAPII pausing release through ETS1 to stimulate angiogenesis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary RNA polymerase II (RNAPII) pausing release is a recently recognized checkpoint for transcriptional regulation. The biological roles of RNAPII pausing release and the mechanisms that by which extracellular signals control it are incompletely understood. Here we identify a novel mechanism by which VEGF stimulates RNAPII pausing-release through acetylation of ETS1, a master endothelial cell transcriptional regulator. In endothelial cells (ECs), ETS1 uniquely bound transcribed gene promoters and stimulated their expression by broadly increasing RNA polymerase II (RNAPII) pause release. VEGF enhanced ETS1 chromatin occupancy. Furthermore, VEGF increased ETS1 acetylation, enhancing its binding by BRD4 and thereby stimulating RNAPII pause release. This ETS1-mediated transduction of VEGF signaling to increase RNAPII pausing release was essential for EC angiogenic responses in vitro and in vivo. Together, our results define a new angiogenic pathway in which VEGF enhances ETS1-Brd4 interaction to broadly promote RNAPII pause release and drive angiogenesis.
Overall design ChiP-seq of ETS1 and Spike-in mRNA seq on HUVEC after VEGF stimulation at 0,1,4,12 hours. ChiP-seq of H3K27ac, H3K27me3, H3K4me1, 2, 3, H3K36me3, c-MYC, RNAPII on HUVEC after VEGF stimulation at 0 hour. ChiP-seq of RNAPII on HUVEC treated with GFP&ETS1 modified RNA, GFP& ETS1 siRNA. ERCC spike-in RNA-seq of HUVEC treated with GFP&ETS1 modified RNA.
Contributor(s) Huan C, Day DS, Fu Y, Sun Y, Wang S, Zhang F, Yan P, Gu F, Stevens SM, Seidman JG, Han Z, Park PJ, Zhang B, Pu WT
Citation(s) 28851877
Submission date Dec 30, 2016
Last update date Jun 05, 2019
Contact name bing zhang
Organization name Shanghai Jiao Tong University
Department Shanghai Center for Systems Biomedicine
Lab Bing Zhang Lab
Street address 800 Dong Chuan Road
City Minhang
State/province Shanghai
ZIP/Postal code 200240
Country China
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (22)
GSM2442773 Brd4-modETS1
GSM2442774 Brd4-modGFP
GSM2442775 ETS1-0hour
BioProject PRJNA359488
SRA SRP095850

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Supplementary file Size Download File type/resource
GSE93030_RAW.tar 13.9 Mb (http)(custom) TAR (of BED)
GSE93030_RNA-seq-fpkm.xlsx 643.8 Kb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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