RT Journal Article
SR Electronic
T1 Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2 (PRC2)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 210542
DO 10.1101/210542
A1 Chul-Hwan Lee
A1 Marlene Holder
A1 Daniel Grau
A1 Ricardo Saldana-Meyer
A1 Rais Ahmad Ganai
A1 Jenny Zhang
A1 Miao Wang
A1 Marc-Werner Dobenecker
A1 Danny Reinberg
A1 Karim-Jean Armache
YR 2017
UL http://biorxiv.org/content/early/2017/10/28/210542.abstract
AB The maintenance of gene expression patterns during metazoan development is carried out, in part, by the actions of the Polycomb Repressive Complex 2 (PRC2). PRC2 catalyzes mono-, di-and trimethylation of histone H3 at lysine 27 (H3K27), with H3K27me2/3 being strongly associated with silenced genes. We demonstrate that EZH1 and EZH2, the two mutually exclusive catalytic subunits of PRC2, are differentially activated by various mechanisms. While both PRC2-EZH1 and PRC2-EZH2 are able to catalyze monomethylation, only PRC2-EZH2 is strongly activated by allosteric modulators and specific chromatin substrates to catalyze di-and trimethylation of H3K27. However, we also show that a PRC2 associated protein, AEBP2, can stimulate the activity of both complexes through a mechanism independent of and additive to allosteric activation. These results have strong implications regarding the cellular requirements for and accompanying adjustments in PRC2 activity, given the difference in the expression of EZH1 and EZH2 upon cellular differentiation.