EZH2, the moderator in the discussion between methyltransferases at histone H3?

Recently, in the January 2014 edition of Molecular Cell, Mozzetta et al. highlighted the importance of enhancer of zeste homolog 2 (EZH2) regulating the interaction between G9a/GLP and polycomb repressive complex 2 (PRC2).PRC2, one of two classes of the polycomb-group (PcG) which form multimeric protein complexes, is involved in maintaining the transcriptional silencing of genes over successive cell cycles (van der Vlag and Otte 1999).PRC2 is composed of proteins SUZ12 (suppressor of zeste 12 homologue), EED (embryonic ectoderm development), RbAp48 (Rb-associated protein 48), and EZH2 (enhancer of zeste homolog 2).Of these core components, the authors found an important EZH2mediated interaction between PRC2 and G9a/GLP.EZH2, a histone-lysine N-methyltransferase, primarily acts to silence genes in many types of cancers (Ren et al. 2012).In the study, the authors show that G9a and GLP proteins are likely to interact with PRC2 via EZH2 Fig. 1.The authors first demonstrated the collaboration between PRC2 and H3K9 and between the PRC2 core components and G9a/GLP methyltransferase by immunopurification analysis in human HeLa cells and mESCs.These results showed that PRC2 core members interact with the main H3K9 KMTs in cells, i.e., G9a, GLP, SETDB1 and Suv39h1.Furthermore, the PRC2 core members co-purified preferentially with G9a and GLP and, at very low levels, with SETDB1 and Suv39h1 (Shinkai and Tachibana 2011).Hence, they decided to focus on G9a and GLP.They purified a recombinant PRC2 complex, performed a pull down assay with GST-G9a/GLP at different concentrations and confirmed a strong interaction among PRC2 and G9a/GLP.They demonstrated that G9a/ GLP and PRC2 both regulate common genes encoding developmental regulators.It also depressed the mESCs lacing G9a