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Series GSE127214 Query DataSets for GSE127214
Status Public on Feb 25, 2020
Title Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation [ChIP-seq]
Organism Rattus norvegicus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in pre-clinical models of heart failure (HF). However, the mechanisms by which BRD4 promotes pathological myocardial fibrosis remain unclear. Here, we demonstrate that BRD4 functions as an effector of TGF-b signaling to stimulate conversion of quiescent cardiac fibroblasts into Periostin (Postn)-positive cells that express high levels of extracellular matrix. BRD4 undergoes stimulus-dependent, genome-wide redistribution in cardiac fibroblasts, becoming enriched on a subset of enhancers and super-enhancers, and leading to RNA polymerase II activation and expression of downstream target genes. Employing the SERTA domain-containing protein 4 (Sertad4) locus as a prototype, we demonstrate that dynamic chromatin targeting of BRD4 is controlled, in part, by p38 mitogen-activated protein kinase, and provide evidence of a novel function for Sertad4 in TGF-b-mediated cardiac fibroblast activation. These findings define BRD4 as a central regulator of the pro-fibrotic cell state of cardiac fibroblasts, and establish a signaling circuit for epigenetic reprogramming in HF.
Overall design ChIP-Seq in ARVFs for Brd4 and RNA PolII
Contributor(s) Stratton MS, Bagchi RA, Hirsch RA, Riching AS, Felisbino MB, Enyart BY, Koch KA, Cavasin MA, Alexanian M, Song K, Qi J, Lemieux ME, Lam MP, Haldar SM, Lin CY, McKinsey TA
Citation(s) 31409188
Submission date Feb 26, 2019
Last update date May 26, 2020
Contact name Timothy McKinsey
Phone 303-724-5479
Organization name University of Colorado Anschutz Medical Campus
Department Division of Cardiology
Lab McKinsey
Street address 12700 E. 19th Ave (8450E)
City Aurora
State/province CO
ZIP/Postal code 80045
Country USA
Platforms (1)
GPL14844 Illumina HiSeq 2000 (Rattus norvegicus)
Samples (6)
GSM3630973 brd4_tgfb
GSM3630974 brd4_veh
GSM3630975 pol2_tgfb
This SubSeries is part of SuperSeries:
GSE127230 Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation
BioProject PRJNA524350
SRA SRP186920

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Supplementary file Size Download File type/resource
GSE127214_RAW.tar 265.0 Mb (http)(custom) TAR (of BED, WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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