DNA microarray analysis of G9a knockout embryonic stem cells

In embryonic stem cells (ESCs), the expression of development-related genes, including germ cellrelated genes, is globally repressed. The transcription factor MAX represses germ cellrelated gene expression in ESCs via PCGF6-polycomb repressive complex (PRC)1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cellrelated 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 the histone methyltransferase SETDB1 cooperatively control germ cellrelated gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cellrelated genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cellrelated genes in ESCs.

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Tatsumi D, Hayashi Y, Endo M, Kobayashi H, Yoshioka T, Kiso K, Kanno S, Nakai Y, Maeda I, Mochizuki K, Tachibana M, Koseki H, Okuda A, Yasui A, Kono T, Matsui Y