Fig. 1.

Dual regulation of histone methylation on H3K9 and H3K27 by G9a. Two proposed mechanisms explain the coordination of H3K9 and H3K27 methylation by the histone methyltransferase G9a to silence an important epithelial marker and tumor suppressor gene E-cadherin. In the first mechanism, G9a physically couples with EZH2 to form a super repression complex to methylate H3K9 and H3K27 simultaneously [72]. In the second mechanism, G9a directly methylates H3K9 and indirectly increases H3K27 methylation via epigenetically upregulating the PCL3 gene to promote the chromatin recruitment of PRC2 and downregulating the KDM7A gene to attenuate the demethylation [67]