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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 [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression 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 |
BMDM from LysM-Cre:NELF-B wt/wt (WT) and/or LysM-Cre:NELF-B fl/fl (NELF-B KO) mice were treated as indicated in individual figure legends (vehicle, LPS, LPS+Dex for 1 h) and RNA was isolated using Qiagen RNA-easy kit. Total RNA was polyA enriched and converted into Illumina-compatible sequencing library with TruSeq mRNA-Seq sample preparation kit (Illumina). Quality control of RNA and libraries was performed using the BioAnalyzer 2100. Pair-end sequencing was performed at the Weill Cornell Epigenomics Core using HiSeq2500.
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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 |
Feb 06, 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 (16)
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| GSM2983148 |
NELF B KO,untreated control [KO_CO_26] |
| GSM2983149 |
WT, LPS, 1h [WT_L60_13] |
| GSM2983150 |
WT, LPS, 1h [WT_L60_77] |
| GSM2983151 |
WT, LPS, 1h [WT_L60_37] |
| GSM2983152 |
KO, LPS, 1h [KO_L60_.5] |
| GSM2983153 |
KO, LPS, 1h [KO_L60_61] |
| GSM2983154 |
KO, LPS, 1h [KO_L60_29] |
| GSM2983155 |
WT, LPS+Dex, 1h [WT_LD60_14] |
| GSM2983156 |
WT, LPS+Dex, 1h [WT_LD60_78] |
| GSM2983157 |
WT, LPS+Dex, 1h [WT_LD60_38] |
| GSM2983158 |
KO, LPS+Dex, 1h [KO_LD60_.6] |
| GSM2983159 |
KO, LPS+Dex, 1h [KO_LD60_62] |
| GSM2983160 |
KO, LPS+Dex, 1h [KO_LD60_30] |
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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 |
PRJNA433244 |
| SRA |
SRP132312 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110243_merged_table_full_02_04_2018_submission.csv.gz |
1.2 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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