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Series GSE64233 Query DataSets for GSE64233
Status Public on Jun 17, 2015
Title Acute TNF-induced repression of cell identity genes is mediated by NFkB-directed redistribution of cofactors from super-enhancers
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in low-grade adipose tissue inflammation and development of insulin resistance during obesity. In this context, nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), is directly involved and required for the acute activation of the inflammatory gene program. Here we show that the major transactivating subunit of NF?B, v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), is also required for acute TNF-induced suppression of adipocyte genes. Notably, this repression does not involve RELA binding to the associated enhancers but rather loss of cofactors and enhancer RNA (eRNA) selectively from high occupancy sites within super-enhancers. Based on these data we have developed models that with high accuracy predict which enhancers and genes are repressed by TNF in adipocytes. We show that these models are applicable to other cell types where TNF represses genes associated with super-enhancers in a highly cell type-specific manner. Our results propose a novel paradigm for NF?B-mediated repression, whereby NF?B selectively redistributes cofactors from high occupancy enhancers, thereby specifically repressing super-enhancer-associated cell identity genes.
Overall design Genome-wide assesment of the acute transcriptional response to TNF in human SGBS adipocytes using RNA- ChIP- and DHS-seq. Total RNA-seq and RNAPII-ChIP seq for vehicle and TNF treated adipocytes are available under GSE60462
Contributor(s) Fisker Schmidt S, Ditlev Larsen B, Loft A, Nielsen R, Grud Skat Madsen J, Mandrup S
Citation(s) 26113076
Submission date Dec 16, 2014
Last update date May 15, 2019
Contact name Susanne Mandrup
Phone +45 6550 2340
Organization name University of Southern Denmark
Department Biochemistry and Molecular Biology
Street address Campusvej 55
City Odense M
ZIP/Postal code 5230
Country Denmark
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (36)
GSM1566728 MED1 ChIP-seq Vehicle Rep1
GSM1566729 MED1 ChIP-seq Vehicle Rep2
GSM1566730 MED1 ChIP-seq TNF Rep1
BioProject PRJNA270506
SRA SRP051211

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource 622.4 Mb (ftp)(http) BW 695.6 Mb (ftp)(http) BW 188.1 Mb (ftp)(http) BW 191.0 Mb (ftp)(http) BW
GSE64233_MED1.peakfile.txt.gz 5.1 Mb (ftp)(http) TXT 220.1 Mb (ftp)(http) BW 231.9 Mb (ftp)(http) BW
GSE64233_MED1_peakfile.txt.gz 4.4 Mb (ftp)(http) TXT 99.7 Mb (ftp)(http) BW 111.9 Mb (ftp)(http) BW
GSE64233_RAW.tar 506.6 Mb (http)(custom) TAR (of BW)
GSE64233_RNA.JQ1.counts.txt.gz 1.1 Mb (ftp)(http) TXT
GSE64233_RNA.KD.counts.txt.gz 1.4 Mb (ftp)(http) TXT
GSE64233_RNA.Pre.counts.txt.gz 597.6 Kb (ftp)(http) TXT
GSE64233_p65.peakfile.txt.gz 1.3 Mb (ftp)(http) TXT 178.7 Mb (ftp)(http) BW 293.5 Mb (ftp)(http) BW
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Raw data are available in SRA
Processed data are available on Series record

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