H3K27me3 regulates macrophage cytokine transcription and impacts on Collagen Induced Arthritis [ChIP-Seq]

The role of epigenetic regulation has been introduced in the process of macrophage polarization and the pathogenesis of inflammatory diseases. As a repressive epigenetic marker, tri-methylation of lysine 27 on histone H3 (H3K27me3) was shown to be important for transcriptional gene expression regulation. Here, we comprehensively analysed H3K27me3 binding promoter sequences by ChIP-seq and corresponding genes function by RNA sequencing in two differentially polarized macrophage populations. The results revealed that H3K27me3 binds on the promoter regions of multiple critical cytokine genes and suppressed their transcription, especially in M-CSF derived macrophages but not GM-CSF derived counterparts. The in vivo study results suggested that symptoms of collagen induced arthritis (CIA) mice can be relieved by reversing the loss of H3K27me3 and reducing IL6 parasecretion of macrophages, suggesting that H3K27me3 might act as a switch in the pathological processes of rheumatoid arthritis (RA). Our results may provide a new approach for the treatment of inflammatory and autoimmune disorders.