Genomics

Dataset Information

39

Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [ChIP_broadly]


ABSTRACT: The M1 and the M2 macrophage polarization programs (activated by IFNγ and IL-4, respectively) lie at the opposite edges of a continuum of activation states but are frequently co-activated during co-infections and in cancer despite controlling divergent functional responses. Whether these two programs are mutually exclusive, how they influence each other, and whether one represents the prevailing response, are all open questions. Co-administration of IFNγ and IL-4 exerted complex inhibitory effects over the M1 and M2 programs at the level of both epigenomic and transcriptional changes. Computational data mining and validation analyses revealed the molecular basis of the differential sensitivity of genes and cis-regulatory elements to the antagonistic effects of the opposite stimulus. For instance, while STAT1 and IRF motifs were associated with robust and IL-4-resistant responses to IFNγ, their coexistence with binding sites for some 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 and the starting point for understanding macrophage responses in complex environmental conditions Overall design: Analysis of transcriptional and epigenomic changes in mouse macrophages stimulated with different cytokines or their combinations

INSTRUMENT(S): Illumina Genome Analyzer II (Mus musculus)

SUBMITTER: Viviana Piccolo  

PROVIDER: GSE84519 | GEO | 2017-03-02

SECONDARY ACCESSION(S): PRJNA329535

REPOSITORIES: GEO

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Publications

Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.

Piccolo Viviana V   Curina Alessia A   Genua Marco M   Ghisletti Serena S   Simonatto Marta M   Sabò Arianna A   Amati Bruno B   Ostuni Renato R   Natoli Gioacchino G  

Nature immunology 20170313 5


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-repressio  ...[more]

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