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胚胎外胚层发育中的表观遗传调控在个体发生过程中的干细胞分化和转化。

Epigenetic regulation of embryonic ectoderm development in stem cell differentiation and transformation during ontogenesis.

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Cell Prolif. 2023 Apr;56(4):e13413. doi: 10.1111/cpr.13413. Epub 2023 Feb 1.

Abstract

Dynamic chromatin accessibility regulates stem cell fate determination and tissue homeostasis via controlling gene expression. As a histone-modifying enzyme that predominantly mediates methylation of lysine 27 in histone H3 (H3K27me1/2/3), Polycomb repressive complex 2 (PRC2) plays the canonical role in targeting developmental regulators during stem cell differentiation and transformation. Embryonic ectoderm development (EED), the core scaffold subunit of PRC2 and as an H3K27me3-recognizing protein, has been broadly implicated with PRC2 stabilization and allosterically stimulated PRC2. Accumulating evidences from experimental data indicate that EED-associating epigenetic modifications are indispensable for stem cell maintenance and differentiation into specific cell lineages. In this review, we discuss the most updated advances to summarize the structural architecture of EED and its contributions and underlying mechanisms to mediating lineage differentiation of different stem cells during epigenetic modification to expand our understanding of PRC2.

摘要

动态染色质可及性通过控制基因表达来调节干细胞命运决定和组织动态平衡。作为一种组蛋白修饰酶,主要介导组蛋白 H3 赖氨酸 27 的甲基化(H3K27me1/2/3),多梳抑制复合物 2(PRC2)在干细胞分化和转化过程中靶向发育调节剂方面发挥着典型作用。胚胎外胚层发育(EED)是 PRC2 的核心支架亚基,也是 H3K27me3 的识别蛋白,广泛参与 PRC2 的稳定和别构刺激 PRC2。越来越多的实验数据表明,EED 相关的表观遗传修饰对于干细胞的维持和分化为特定的细胞谱系是必不可少的。在这篇综述中,我们讨论了最新的进展,以总结 EED 的结构架构及其在不同干细胞的谱系分化中的贡献和潜在机制,以扩大我们对 PRC2 的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f6/10068960/d968a619cc17/CPR-56-e13413-g005.jpg

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