Polycomblike家族蛋白参与表观遗传调控的分子机制及其生物学意义  

Molecular mechanisms of the Polycomblike family proteins in epigenetic regulation and their biological functions

作　　者：周海霞 王占新 Zhou HaiXia;Wang ZhanXin(Key Laboratory of Cell Proliferation and Regulation Biology,Ministry of Education,College of Life Sciences,Beijing Normal University,Beijing 100875,China)

机构地区：[1]北京师范大学生命科学学院,细胞增殖及调控生物学教育部重点实验室,北京100875

出　　处：《中国科学：生命科学》2022年第8期1118-1128,共11页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:31870725,32071204);国家杰出青年科学基金(批准号:32125008)资助。

摘　　要：PRC2复合物是Polycomb家族蛋白的重要复合物之一,在细胞的增殖、分化和谱系特征的维持等生理过程中发挥着至关重要的作用.PRC2主要通过修饰染色质和调控染色质结构的方式对基因表达起抑制作用,其中PRC2的核心组分EZH2在组蛋白H3第27位赖氨酸上留下的三甲基化修饰(H3K27me3)是与基因抑制相关的重要标记之一.PRC2的核心组分需要与其他结合蛋白结合形成全酶才能发挥出最大催化活性.PRC2的结合蛋白,例如Polycomblike(PCL)蛋白,对PRC2的功能起着重要的调控作用.近些年的研究表明,PCL蛋白对PRC2的活性和其在染色质上的招募起着重要的调控作用.此外,PCL蛋白的表达异常与多种人类癌症相关.因此PCL蛋白结构与功能的研究对深入了解其调控PRC2的机制以及靶向PCL相关的药物研发均具重要意义.本文就近年来关于PCL蛋白的结构和功能研究进展进行总结,着重阐述人源PCL蛋白的分子机制和生物学功能.The PRC2 complex is a major complex in the Polycomb group of proteins.It plays an essential role in cell proliferation,differentiation,and the maintenance of cellular identity.PRC2 functions in gene repression mainly by modifying chromatin and regulating chromatin structure,among which the tri-methylation mark on histone H3 at Lys27(H3 K27 me3)added by EZH2,the core PRC2 component,is a hallmark of gene repression.PRC2 core components must bind PRC2-associated proteins to form a holoenzyme and become fully active.PRC2-associated proteins,such as Polycomblike(PCL)proteins,are important in regulating the function of PRC2.Recent studies have revealed that human PCL proteins play key roles in regulating the activity and the recruitment of chromatin by PRC2.In addition,PCL proteins are closely related to several human cancers.Thus,advances in the structure and function of PCL proteins would facilitate our understanding of their roles in PRC2 regulation and would expedite the development of strategies for therapeutically targeting PCL-related cancers.In this review,we summarize recent progress on the structure and function of PCL proteins,with an emphasis on the molecular mechanisms and biological functions of human PCL proteins.

关 键 词：PCL家族蛋白 表观遗传调控 PRC2复合物 细胞记忆 招募 

分 类 号：Q75[生物学—分子生物学]