PDF(Pubmed)
Abstract：
Cell fate determination is an intricate process which is orchestrated by multiple regulatory layers including signal pathways, transcriptional factors, epigenetic modifications, and metabolic rewiring. Among the sophisticated epigenetic modulations, the repressive mark H3K27me3, deposited by PRC2 (polycomb repressive complex 2) and removed by demethylase KDM6, plays a pivotal role in mediating the cellular identity transition through its dynamic and precise alterations. Herein, we overview and discuss how H3K27me3 and its modifiers regulate pluripotency maintenance and early lineage differentiation. We primarily highlight the following four aspects: 1) the two subcomplexes PRC2.1 and PRC2.2 and the distribution of genomic H3K27 methylation; 2) PRC2 as a critical regulator in pluripotency maintenance and exit; 3) the emerging role of the eraser KDM6 in early differentiation; 4) newly identified additional factors influencing H3K27me3. We present a comprehensive insight into the molecular principles of the dynamic regulation of H3K27me3, as well as how this epigenetic mark participates in pluripotent stem cell-centered cell fate determination.
摘要：
细胞命运决定是一个复杂的过程，由多个调控层协调，包括信号通路，转录因子，表观遗传修饰,和代谢重新布线。在复杂的表观遗传调制中，抑制标记H3K27me3由PRC2（多梳状抑制复合物2）沉积，并由去甲基酶KDM6去除，通过其动态和精确的改变在介导细胞身份转换中起关键作用。在这里，我们概述并讨论了H3K27me3及其修饰剂如何调节多能性维持和早期谱系分化。我们主要强调以下四个方面：1）两个亚复合物PRC2.1和PRC2.2以及基因组H3K27甲基化的分布；2）PRC2作为多能性维持和退出的关键调节因子；3）橡皮擦KDM6在早期分化中的新兴作用；4）新发现的影响H3K27me3的其他因素。我们对H3K27me3动态调节的分子原理以及这种表观遗传标记如何参与以多能干细胞为中心的细胞命运决定进行了全面的了解。
