Regulation of histone methylation by automethylation of PRC2

• DOI: 10.1101/gad.328849.119
• Publication Date: 2019-09-05T18:45:19Z
• Authors: Xueyin Wang; Yicheng Long; Richard D. Paucek; Anne R. Gooding; Thomas Lee; Rachel M. Burdorf; Thomas R. Cech
• Keywords: PRC2; Histone Methylation

Polycomb-repressive complex 2 (PRC2) is a histone methyltransferase that critical for regulating transcriptional repression in mammals. Its catalytic subunit, EZH2, responsible the trimethylation of H3K27 and also undergoes automethylation. Using mass spectrometry analysis recombinant human PRC2, we identified three methylated lysine residues (K510, K514, K515) on disordered but highly conserved loop EZH2. Methylation these lysines increases PRC2 activity, whereas their mutation decreases activity vitro. De novo methylation an EZH2 knockout cell line greatly impeded by automethylation lysines. occurs intramolecularly (in cis) pseudosubstrate sequence flexible loop. This posttranslational modification cis regulation are analogous to activation many protein kinases autophosphorylation. We propose allows modulate its sensing H3 tails, SAM concentration, perhaps other effectors.