Authors
Delphine Douillet, Christie C Sze, Caila Ryan, Andrea Piunti, Avani P Shah, Michal Ugarenko, Stacy A Marshall, Emily J Rendleman, Didi Zha, Kathryn A Helmin, Zibo Zhao, Kaixiang Cao, Marc A Morgan, Benjamin D Singer, Elizabeth T Bartom, Edwin R Smith, Ali Shilatifard
Publication date
2020/6
Journal
Nature genetics
Volume
52
Issue
6
Pages
615-625
Publisher
Nature Publishing Group US
Description
The COMPASS protein family catalyzes histone H3 Lys 4 (H3K4) methylation and its members are essential for regulating gene expression. MLL2/COMPASS methylates H3K4 on many developmental genes and bivalent clusters. To understand MLL2-dependent transcriptional regulation, we performed a CRISPR-based screen with an MLL2-dependent gene as a reporter in mouse embryonic stem cells. We found that MLL2 functions in gene expression by protecting developmental genes from repression via repelling PRC2 and DNA methylation machineries. Accordingly, repression in the absence of MLL2 is relieved by inhibition of PRC2 and DNA methyltransferases. Furthermore, DNA demethylation on such loci leads to reactivation of MLL2-dependent genes not only by removing DNA methylation but also by opening up previously CpG methylated regions for PRC2 recruitment, diluting PRC2 at Polycomb …
Scholar articles
D Douillet, CC Sze, C Ryan, A Piunti, AP Shah… - Nature genetics, 2020