Genome-wide profiles of IRF8 and PU.1 bindings, and H3K4me1 and H3K27ac histone marks in wild-type and IRF8-knockout microglia [CHIP-seq]
The role of the lineage-determining transcription factor Interferon regulatory factor 8 (IRF8) in microglia remains elucidated. Here we report the genome-wide IRF8 binding profiles in microglia at various ages. CUT&RUN methodology revealed that IRF8 starts to bind to the genome around postnatal day 9 (P9), and its number increases with age. In comparison to peritoneal macrophages, microglia IRF8 showed a cell-intrinsic binding pattern. By co-occurrence analysis, most IRF8 was H3K4me1/H3K27ac-marked enhancers, and many of them bind to the H3K27ac(high) super-enhancer regions. In IRF8KO microglia, H3K4me1 and H3K27ac profiles were altered and deposited aberrantly on the genome. This study provides a novel insight into understanding epigenetic regulation in microglia. Overall design: Analyzed IRF8 binding profile in WT P9, three P14, adult microglia, and peritoneal macrophages using CUT&RUN. Additionally, profiles of PU.1 binding, H3K4me1, and H3K27ac histone marks in adult microglia in the presence or absence of IRF8 were analyzed similarly. Four corresponding IgG controls were included.