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IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [ChIP-seq]

ABSTRACT: Mechanisms by which IFN-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an ‘M2’-like homeostatic/reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF. Mechanistically, IFN-γ ‘disassembled’ a subset of enhancers by inducing coordinate suppression of binding by MAF, lineage-determining transcription factors, and chromatin accessibility. Genes associated with MAF-binding disassembled enhancers were suppressed in rheumatoid arthritis macrophages, revealing a disease-associated ‘negative IFN-γ signature’. These results identify enhancer inactivation and disassembly as a mechanism of IFN-γ-mediated gene repression, and MAF as a regulator of the macrophage enhancer landscape that is suppressed by IFN-γ to augment macrophage activation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98367 | GEO | 2017/07/01

SECONDARY ACCESSION(S): PRJNA384909

REPOSITORIES: GEO

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IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [RNA-seq]

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