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Series GSE109131 Query DataSets for GSE109131
Status Public on Feb 28, 2018
Title Gene-specific mechanisms dictate glucocorticoid receptor-mediated repression of inflammatory response genes in macrophages [ChIP-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The Glucocorticoid Receptor (GR) potently represses macrophage-elicited inflammation, however, the underlying mechanisms remain obscure. Our genome-wide analysis reveals that pro-inflammatory paused genes, activated via global negative elongation factor (NELF) dissociation and RNA Polymerase (Pol)2 release from early elongation arrest, and non-paused genes, induced by de novo Pol2 recruitment, are equally susceptible to acute glucocorticoid repression. Moreover, in both cases the dominant mechanism involves rapid GR tethering to p65 at NF-kB binding sites. Yet, specifically at paused genes, GR activation triggers widespread promoter accumulation of NELF, with myeloid cell-specific NELF deletion conferring glucocorticoid resistance. Conversely, at non-paused genes, GR attenuates the recruitment of p300 and histone acetylation, leading to a failure to assemble BRD4 and Mediator at promoters and enhancers, ultimately blocking Pol2 initiation. Thus, GR displays no preference for a specific pro-inflammatory gene class, however, it effects repression by targeting distinct temporal events and components of transcriptional machinery
Overall design ChIPSeq experiments in primarry mouse bone marrow derived macrophages (BMMF) from the wild-type (C57BL/6 mice (NCI, Charles River Laboratories)) mice treated with LPS,Dex or LPS+Dex in comparision with untreated control to determine genome-wide distribution of RNA polymerase II, Glucocorticoid receptors (GR), transcription factor NFkB, NELFE and BRD4.
Please note that 32_p65_Input.bam was used as an input in the Brd4 experiment
Contributor(s) Sacta MA, Tharmalingam B, Coppo M, Rollins DA, Deochand DK, Benjamin B, Yu L, Zhang B, Hu X, Li R, Chinenov Y, Rogatsky I
Citation(s) 29424686
Submission date Jan 12, 2018
Last update date Mar 21, 2019
Contact name Yurii Chinenov
Organization name Hospital for special surgery
Department Research Division
Lab HSS Genomics Center
Street address 535 E 71 str, Hospital for Special Surgery
City New york
State/province New York
ZIP/Postal code 11361
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (33)
GSM2932659 01_BRD4_L_rep1
GSM2932660 02_BRD4_L_rep2
GSM2932661 03_BRD4_LD_rep1
This SubSeries is part of SuperSeries:
GSE110279 Gene-specific mechanisms dictate glucocorticoid receptor-mediated repression of inflammatory response genes in macrophages
BioProject PRJNA429743
SRA SRP128988

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Supplementary file Size Download File type/resource
GSE109131_RAW.tar 12.4 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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