GSE151481
Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [ChIP-Seq]
Currently, the epigenetic mechanisms governing the osteoclast differentiation process remains poorly understood. To investigate the combinatorial activity of TFs, cis-regulatory elements, and the enhancer landscape that establish and maintain osteoclast transcriptional identity, we profiled histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3) and PU.1 and IRF8 binding by ChIP-seq. RNA-seq data from sorted Ly6Chi, Ly6Cint, and Ly6C– cells were overlaid with ChIP-seq data to identify epigenetic changes specific to each subset and genotype. Our data suggest that the Ly6Chi inflammatory monocytes and Ly6Cint cells are transcriptionally and epigenetically programmed to differentiate in mature osteoclasts when compared to Ly6C– anti-inflammatory monocytes. A combinatorial activity of TFs and cis-regulatory elements in the vicinity of several osteoclast-specific genes are responsible for establishing and maintaining osteoclast identity in these subsets. In Irf8 cKO mice, several promoters and enhancers established during the progenitor stage may be critical for initiating early lineage commitment and priming monocyte subsets to differentiate into robust osteoclasts. Overall design: ChIP-seq analysis of epigenetic changes in BMMs stimulated with MCSF (day 0) and OCs stimulated with MCSF plus RANKL (day 4). We performed ChIP-seq for H3K4me1, H3K4me3, H3K27ac, H3K27me3, and PU.1 in BMMs and OCs. Both male and female mice and cells obtained from both genders were analyzed in this study.