澳大利亚莫纳什大学Chen Davidovich等研究人员合作揭示EZH2中核糖体相互作用表面不可分离的RNA结合和染色质修饰活性。这一研究成果于2024年5月14日在线发表在国际学术期刊《自然—遗传学》上。

据介绍，PRC2在细胞中与RNA相互作用，但对于RNA如何调控PRC2的典型功能（包括染色质修饰和维持品系定向细胞中的转录程序）还没有达成共识。

附：英文原文

Title: Inseparable RNA binding and chromatin modification activities of a nucleosome-interacting surface in EZH2

Author: Gail, Emma H., Healy, Evan, Flanigan, Sarena F., Jones, Natasha, Ng, Xiao Han, Uckelmann, Michael, Levina, Vitalina, Zhang, Qi, Davidovich, Chen

Issue&Volume: 2024-05-14

Abstract: Polycomb repressive complex 2 (PRC2) interacts with RNA in cells, but there is no consensus on how RNA regulates PRC2 canonical functions, including chromatin modification and the maintenance of transcription programs in lineage-committed cells. We assayed two separation-of-function mutants of the PRC2 catalytic subunit EZH2, defective in RNA binding but functional in methyltransferase activity. We find that part of the RNA-binding surface of EZH2 is required for chromatin modification, yet this activity is independent of RNA. Mechanistically, the RNA-binding surface within EZH2 is required for chromatin modification in vitro and in cells, through interactions with nucleosomal DNA. Contrarily, an RNA-binding-defective mutant exhibited normal chromatin modification activity in vitro and in lineage-committed cells, accompanied by normal gene repression activity. Collectively, we show that part of the RNA-binding surface of EZH2, rather than the RNA-binding activity per se, is required for the histone methylation in vitro and in cells, through interactions with the substrate nucleosome.

DOI: 10.1038/s41588-024-01740-8

Source: https://www.nature.com/articles/s41588-024-01740-8