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- W2770530503 abstract "The cytokines interleukin 1β and 6 (IL-1β, IL-6) mediate the acute phase response (APR). In liver, they regulate the secretion of acute phase proteins. Using RNA-seq in primary hepatocytes, we show that these cytokines regulate transcription in a bifurcated manner, leading to both synergistic and antagonistic gene expression. By mapping changes in enhancer landscape and transcription factor occupancy (using ChIP-seq), we show that synergistic gene induction is achieved by assisted loading of STAT3 on chromatin by NF-κB. With IL-6 treatment alone, STAT3 does not efficiently bind 20% of its coordinated binding sites. In the presence of IL-1β, NF-κB is activated, binds a subset of enhancers and primes their activity, as evidenced by increasing H3K27ac. This facilitates STAT3 binding and synergistic gene expression. Our findings reveal an enhancer-specific crosstalk whereby NF-κB enables STAT3 binding at some enhancers while perturbing it at others. This model reconciles seemingly contradictory reports of NF-κB-STAT3 crosstalk." @default.
- W2770530503 created "2017-12-04" @default.
- W2770530503 creator A5023528108 @default.
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- W2770530503 creator A5046734058 @default.
- W2770530503 creator A5068240181 @default.
- W2770530503 date "2017-11-29" @default.
- W2770530503 modified "2023-10-17" @default.
- W2770530503 title "Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading" @default.
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- W2770530503 doi "https://doi.org/10.1038/s41467-017-02055-5" @default.
- W2770530503 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5707366" @default.
- W2770530503 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29185442" @default.
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