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- W2596838981 abstract "Natoli and colleagues reveal the epigenomic and transcriptional bases for gene-specific cross-repression of the cytokines IFN-γ and IL-4 in macrophages. Stimulation of macrophages with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer, macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited the epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while binding motifs for the transcription factors STAT1 and IRF1 were associated with robust and IL-4-resistant responses to IFN-γ, their coexistence with binding sites for auxiliary transcription factors such as AP-1 generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation in complex environmental conditions." @default.
- W2596838981 created "2017-03-23" @default.
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- W2596838981 date "2017-03-13" @default.
- W2596838981 modified "2023-10-05" @default.
- W2596838981 title "Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk" @default.
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- W2596838981 doi "https://doi.org/10.1038/ni.3710" @default.
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