美国加州大学伯克利分校Eva Nogales研究组发现，在H2AK119ub1和其他组蛋白修饰的存在下，JARID2和AEBP2调节PRC2。该研究于2021年1月22日发表于国际一流学术期刊《科学》上。

据研究人员介绍，多梳抑制复合物1和2（PRC1和PRC2）通过表观遗传基因表达调控共同确定细胞身份。但是，通过PRC1介导的H2AK119ub1识别PRC2募集的机制仍然知之甚少。

PRC2与辅因子JARID2和AEBP2结合到含H2AK119ub1核小体的冷冻电镜结构揭示出EZH2的桥螺旋结构，其连接SET结构域、H3尾部和核小体DNA。JARID2和AEBP2各自与一个泛素和H2A-H2B表面相互作用。JARID2通过与多梳蛋白EED和H2AK119-泛素相互作用而刺激PRC2，而AEBP2具有额外的支架作用。这些辅助因子的存在部分克服了H3K4me3和H3K36me3对核心PRC2的抑制作用（在没有辅助因子的情况下）。

这些结果支持JARID2和AEBP2在组蛋白修饰和PRC2活性之间的相互影响中起关键作用。

附：英文原文

Title: JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications

Author: Vignesh Kasinath, Curtis Beck, Paul Sauer, Simon Poepsel, Jennifer Kosmatka, Marco Faini, Daniel Toso, Ruedi Aebersold, Eva Nogales

Issue&Volume: 2021/01/22

Abstract: Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition of PRC1-mediated H2AK119ub1 remains poorly understood. Our PRC2 cryo–electron microscopy structure with cofactors JARID2 and AEBP2 bound to a H2AK119ub1-containing nucleosome reveals a bridge helix in EZH2 that connects the SET domain, H3 tail, and nucleosomal DNA. JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface. JARID2 stimulates PRC2 through interactions with both the polycomb protein EED and the H2AK119-ubiquitin, whereas AEBP2 has an additional scaffolding role. The presence of these cofactors partially overcomes the inhibitory effect that H3K4me3 and H3K36me3 exert on core PRC2 (in the absence of cofactors). Our results support a key role for JARID2 and AEBP2 in the cross-talk between histone modifications and PRC2 activity.

DOI: 10.1126/science.abc3393

Source: https://science.sciencemag.org/content/371/6527/eabc3393