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Series GSE53998 Query DataSets for GSE53998
Status Public on Sep 29, 2014
Title NF-kB coordinates rapid, BRD4-dependent remodeling of proinflammatory super-enhancers [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Proinflammatory stimuli rapidly and globally remodel chromatin landscape, thereby enabling transcriptional responses. Yet, the mechanisms coupling chromatin regulators to the master regulatory inflammatory transcription factor NF-kB remain poorly understood.  We report in human endothelial cells (ECs) that activated NF-kB binds to enhancers, provoking a rapid, global redistribution of BRD4 preferentially at super-enhancers, large enhancer domains highly bound by chromatin regulators.  Newly established NF-kB super-enhancers drive nearby canonical inflammatory response genes. In both ECs and macrophages BET bromodomain inhibition prevents super-enhancer formation downstream of NF-kB activation, abrogating proinflammatory transcription. In TNFa-activated endothelium this culminates in functional suppression of leukocyte rolling, adhesion and transmigration.  Sustained BET bromodomain inhibitor treatment of LDLr -/- animals suppresses atherogenesis, a disease process rooted in pathological vascular inflammation involving endothelium and macrophages. These data establish BET-bromodomains as key effectors of inflammatory response through their role in the dynamic, global reorganization of super-enhancers during NF-kB activation.  
 
Overall design ChIP-Seq for various transcription factors, RNA Polymerase II, and histone modifications in human endothelial cells
 
Contributor(s) Brown JD, Lin CY, Bradner JE
Citation(s) 25263595
Submission date Jan 10, 2014
Last update date May 15, 2019
Contact name James Bradner
E-mail(s) bradner_computation@dfci.harvard.edu
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Bradner Lab
Street address 450 Brookline
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (21)
GSM1305201 EC_BRD4_CON
GSM1305202 EC_BRD4_TNF
GSM1305203 EC_BRD4_TNF_JQ1
This SubSeries is part of SuperSeries:
GSE54000 NF-kB coordinates rapid, BRD4-dependent remodeling of proinflammatory super-enhancers
Relations
BioProject PRJNA234305
SRA SRP035320

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE53998_RAW.tar 1.5 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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