多梳抑制复合体PRC1的核心组分CBX家族蛋白在表观遗传调控中的作用(英文)

Epigenetic regulation by polycomb group complexes:focus on roles of CBX proteins

研究目的:多梳蛋白家族(PcG)是一类染色质水平上通过表观遗传修饰调控靶基因的转录因子,其主要功能是使其靶基因转录受到抑制进而沉默。PcG通常以多梳蛋白复合体(PRC)的形式存在,目前研究的最多的是PRC1和PRC2。PRC1在PcG对其靶基因进行转录抑制发挥着主要作用。本综述主要论述了哺乳动物中PRC1核心成员CBX蛋白在多梳蛋白调控基因转录过程中发挥的作用及其对胚胎发育、细胞记忆、细胞周期、细胞增殖和肿瘤形成等过程的影响。创新要点:现已有大量有关PcG在表观遗传水平对其靶基因进行修饰转录机制的综述报道,且以PRC1和PRC2为整体来介绍表观遗传调控机制的文章也屡见不鲜。然而,关于PRC1核心成员CBX蛋白在哺乳动中的同源蛋白CBX2、CBX4、CBX6、CBX7、CBX8对哺乳动物个体发育调节及肿瘤发生过程的分子机制并没有系统的论述。本综述主要将这五种CBX蛋白在转录分子水平上的所发挥的功能进行相关的介绍,并且总结了CBX2、CBX4、CBX6、CBX7、CBX8各自最新的研究进展,体现出五种CBX蛋白的共同功能、各自独特的功能及彼此间的相互联系。重要结论:总结了在哺乳动物中的五种CBX蛋白在胚胎发育和肿瘤形成等过程中独特的功能调节机制以及整体的相互作用,发现CBX作为PRC1的核心组分在基因表观遗传调控中发挥着极其重要的作用。

Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.