3 years ago

Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2 (PRC2)

K.-J., Ganai, Holder, Saldana-Meyer, Lee, M., R., C.-H., Reinberg, Dobenecker, D., Armache, M.-W., Grau, Wang, J., R. A., Zhang
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.

Publisher URL: http://biorxiv.org/cgi/content/short/210542v1

DOI: 10.1101/210542

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.