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| Status |
Public on Feb 09, 2017 |
| Title |
Inhibition of inflammatory gene transcription by IL-10 is associated with rapid suppression of LPS-induced enhancer activation [stat3_ChIP] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
IL-10 limits the magnitude of inflammatory gene expression following microbial stimuli and is essential to prevent inflammatory disease, however, the molecular basis for IL-10 mediated inhibition remains elusive. Using a genome-wide approach we demonstrate that inhibition of transcription is the primary mechanism for IL-10-mediated suppression in LPS-stimulated macrophages, and that inhibited genes can be divided into two clusters. Genes in the first cluster are inhibited only if IL-10 is included early in the course of LPS stimulation and is strongly enriched for interferon-inducible genes. Genes in the second cluster can be rapidly suppressed by IL-10 even after transcription is initiated, and this is associated with suppression of LPS-induced enhancer activation. Interestingly, the ability of IL-10 to rapidly suppress active transcription exhibits a delay following LPS stimulation. Thus, a key pathway for IL-10 mediated suppression involves rapid inhibition of enhancer function during the secondary phase of the response to LPS.
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| Overall design |
Murine bone marrow derived macrophage pools were stimulated with IL-10 for 30 min, LPS for 195 min, or LPS for 195 min with the adddition of IL-10 for the last 30 min. ChIP-Seq performed for STAT3
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| Contributor(s) |
Conaway EA, de Oliveira DC, McInnis C, Snapper S, Horwitz BH |
| Citation(s) |
28213503 |
| Submission date |
Aug 29, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Bruce Horwitz |
| E-mail(s) |
bhorwitz@rics.bwh.harvard.edu
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| Organization name |
Brigham and Women's Hospital
|
| Department |
Pathology
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| Street address |
77 Ave Louis Pasteur
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE86170 |
Inhibition of inflammatory gene transcription by IL-10 is associated with rapid suppression of LPS-induced enhancer activation |
|
| Relations |
| BioProject |
PRJNA340446 |
| SRA |
SRP083193 |
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