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| 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
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| 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
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| 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
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| 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 |
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| Submission date |
Jan 12, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Yurii Chinenov |
| Organization name |
Hospital for special surgery
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| Department |
Research Division
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| Lab |
HSS Genomics Center
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| Street address |
535 E 71 str, Hospital for Special Surgery
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| City |
New york |
| State/province |
New York |
| ZIP/Postal code |
11361 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (33)
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| This SubSeries is part of SuperSeries: |
| GSE110279 |
Gene-specific mechanisms dictate glucocorticoid receptor-mediated repression of inflammatory response genes in macrophages |
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| Relations |
| BioProject |
PRJNA429743 |
| SRA |
SRP128988 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE109131_RAW.tar |
12.4 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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