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| Status |
Public on Jun 20, 2019 |
| Title |
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate M1-like macrophage polarization [RNA-seq II] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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 |
RNA-seq analysis of transcriptional changes in human macrophages (M-CSF/GM-CSF) that were cultured with or without IFN-γ and then stimulated with LPS or vice versa
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| |
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| Contributor(s) |
Bachu M, Ivashkiv L |
| Citation(s) |
31346169 |
| |
| Submission date |
May 01, 2019 |
| Last update date |
Sep 19, 2019 |
| Contact name |
Mahesh Bachu |
| E-mail(s) |
bmahesh07@gmail.com, bachum@hss.edu
|
| Organization name |
Hospital For Special Surgery
|
| Street address |
535 E 70th St 6th Floor
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (24)
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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 |
PRJNA540657 |
| SRA |
SRP194387 |
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