Genome-wide analysis of PGC-1α-binding in microglia

PGC-1α in microglia protects against ischemia-induced brain damage in mice. The data suggest that microglia-specific PGC-1α play a key role in limiting ischemia-induced brain damage and potently participates in regulating microglial function. To further clarify the mechanism of PGC-1α, we conducted chromatin immunoprecipitation-sequencing (ChIP-Seq) analysis to identify the targets of PGC-1α in microglia from mPGC-1α mice at 24 h after ischemic stroke. KEGG pathway analysis of these genes identified the mitophagy signaling pathway as one of the most highly enriched pathways. Finally, we demonstrated that PGC-1α induces mitophagy by regulating ULK1 expression in an ERRα-dependent manner, thereby reducing neuroinflammatory reactions. Primary microglia were isolated from mPGC-1α mice at 24 h after ischemic stroke using the MojoSortTM mouse P2RY12 selection kit (Biolegend, San Diego, CA, USA) according to the manufacturer’s protocol. Then the samples were processed to perform ChIP-Seq analysis.