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| Status |
Public on Jun 12, 2019 |
| Title |
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate M1-like macrophage polarization [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-γ and LPS. Synergistic activation of canonical inflammatory NF-κB target genes by IFN-γ and LPS is well appreciated, but less is known about whether IFN-γ negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-γ selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-γ-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-γ-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-γ. These findings reveal that IFN-γ suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-γ selectively inhibits TLR4-induced transcription.
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| Overall design |
ChIP-seq analysis of epigenomic changes in human macrophages that were cultured with or without IFN-γ and then stimulated with LPS
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| |
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| Contributor(s) |
Ivashkiv L, Kang K, Kang K |
| Citation(s) |
31346169 |
| |
| Submission date |
Oct 08, 2018 |
| Last update date |
Sep 19, 2019 |
| Contact name |
Keunsoo Kang |
| E-mail(s) |
kangk1204@gmail.com
|
| Organization name |
Dankook University
|
| Street address |
119 Dandae-ro
|
| City |
Cheonan |
| ZIP/Postal code |
31119 |
| Country |
South Korea |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (21)
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| This SubSeries is part of SuperSeries: |
| GSE120945 |
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate M1-like macrophage polarization |
|
| Relations |
| BioProject |
PRJNA495074 |
| SRA |
SRP164577 |
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