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Environment Drives Selection and Function of Enhancers Controlling Tissue-Specific Macrophage Identities

ABSTRACT: Macrophages reside in essentially all tissues of the body and play key roles in innate and adaptive immune responses. Distinct populations of tissue macrophages also acquire context-specific functions that are important for normal tissue homeostasis. To investigate mechanisms responsible for tissue-specific functions, we analyzed the transcriptomes and enhancer landscapes of brain microglia and resident macrophages of the peritoneal cavity. In addition, we exploited natural genetic variation as a genome-wide “mutagenesis” strategy to identify DNA recognition motifs for transcription factors that promote common or subset-specific binding of the macrophage lineage-determining factor PU.1. We find that distinct tissue environments drive divergent programs of gene expression by differentially activating a common enhancer repertoire and by inducing the expression of divergent secondary transcription factors that collaborate with PU.1 to establish tissue-specific enhancers. These findings provide insights into molecular mechanisms by which tissue environment influences macrophage phenotypes that are likely to be broadly applicable to other cell types.

ORGANISM(S): Mus musculus

PROVIDER: GSE62826 | GEO | 2014/12/04

SECONDARY ACCESSION(S): PRJNA265386

REPOSITORIES: GEO

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Environment Drives Selection and Function of Enhancers Controlling Tissue-Specific Macrophage Identities

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