小柯机器人

美国西北大学Feinberg医学院Ali Shilatifard课题组揭示，COMPASS、Polycomb以及DNA甲基化之间的平衡如何调节发育基因表达过程中的组蛋白H3K4三甲基化。这一研究成果于2020年5月11日在线发表在《自然—遗传学》上。

Title: Uncoupling histone H3K4 trimethylation from developmental gene expression via an equilibrium of COMPASS, Polycomb and DNA methylation

Author: 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

Issue&Volume: 2020-05-11

Abstract: 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-repressed genes. These findings reveal how the context and function of these three epigenetic modifiers of chromatin can orchestrate transcriptional decisions and demonstrate that prevention of active repression by the context of the enzyme and not H3K4 trimethylation underlies transcriptional regulation on MLL2/COMPASS targets.

DOI: 10.1038/s41588-020-0618-1

Source: https://www.nature.com/articles/s41588-020-0618-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex