Genomics

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Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [ATAC-seq]


ABSTRACT: Microglia are versatile regulators in brain development and disorders. Emerging evidence links miRNA-mediated regulation to microglial function; however, the exact underlying mechanism remains largely unknown. Here, we discover that miR-137, a neuropsychiatric disorders-associated miRNA, is abundant in the microglial nucleus and exhibits unexpected epigenetic functions in maintaining the global transcriptomic state, core properties, and functions of microglia. Mechanistically, microglial Mir137 deletion increases the accessibility of chromatin, which harbors binding motifs of microglial master transcription factor Pu.1. Our biochemical and bioinformatics analyses suggest that miR-137 can interact with Pu.1, thus influencing Pu.1-mediated gene expression. Importantly, we find that increased Pu.1 binding upregulates the target gene Jdp2, and Jdp2 knockdown markedly suppresses the impaired cellular phenotypes in Mir137 knockout microglia. Collectively, our study provides evidence supporting a notion that miR-137 acts as an epigenetic regulator, and this microglia-specific function is essential to maintain normal adult brain function.

ORGANISM(S): Mus musculus

PROVIDER: GSE222662 | GEO | 2024/02/22

REPOSITORIES: GEO

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