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BRD8通过感知和维持素乙化,保护多能状态

Li Sun¹, Xiuling Fu¹, Zhen Xiao¹

¹Department of Systems Biology, Southern University of Science and Technology, Shenzhen, 518055, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|December 10, 2024

概括

基因素乙转移酶读取器BRD8通过调节基因素乙化来维持细胞稳定性. 减少BRD8表达会损害原始到纯粹的干细胞转化,揭示了它在细胞命运中的作用.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
发展生物学发展生物学
干细胞生物学干细胞生物学

背景情况:

表观遗传机制对于维持细胞命运稳定性和引导胚胎发育过程中的分化至关重要.
表观遗传调节者的精确作用,比如氨酸转移酶读者蛋白,在控制细胞转换方面仍然不完全理解.

研究的目的:

为了研究BRD8的功能,一个酸转移酶读者蛋白质,在原始小鼠表皮质干细胞 (EpiSCs) 和原始小鼠胚胎干细胞 (ESCs) 之间的转化.
阐明BRD8在细胞命运过渡期间影响染色质状态和基因表达的分子机制.

主要方法:

通过CRISPR介导的基因编辑来减少小鼠EpiSCs中的Brd8表达.
染色体免疫沉测序 (ChIP-seq) 用于评估基因素乙化和染色体可访问性.
分析与原始和天真细胞状态相关的基因表达模式.

主要成果:

减少Brd8表达影响了原始化EpiSCs转化为天真ESCs的转化.
BRD8在促进体和基因体中保持了基因素乙化,有助于在体基因中开放色素和在纯粹特异性基因中保持基因素乙化.
降低Brd8水平导致原始特异性基因的组素乙化减少,并加速了原始特异性基因的染色质可访问性变化.
鉴定出活性素脱甲基化是有效的原始细胞转化为原始细胞转化的一个要求.

结论:

BRD8 作为一个关键的表观遗传调节器,它读取 histone 乙化状态以控制细胞命运的稳定性.
蛋白质BRD8影响基因组范围内的基因组乙转移酶KAT5的结合,影响色素动态.
这项研究揭示了BRD8在读取基因素乙化中的功能如何使干细胞分化和细胞类型转换成为可能和阻碍.

关键词:

在这种情况下,染色染色素表观遗传学是指表观遗传学.基因素乙化基因素乙化基因素乙化多能干细胞是一种多能干细胞.

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