DNMTs function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells

In embryonic stem cells (ESCs), the expression of development-related genes, including germ cell-related genes, is globally repressed. The transcription factor MAX represses germ cell-related gene expression in ESCs via PCGF6-polycomb repressive complex (PRC) 1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cell-related gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and cooperatively controlled germ cell-related gene expression in ESCs. To elucidate the significance of functional interactions between MAX and DNMTs on a genome-wide level, we performed targeted methylome sequencing (TMS) for semi-comprehensive DNA methylome analysis of Max-Knockdown ESCs and a differentially methylated region (DMR) calling identified 17 genes which had hypomethylated DMRs in the proximity of TSSs compared with control ESCs. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cell-related genes in ESCs.