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H2Bub1沉积复合物是人类和小鼠心脏生成所需的

Syndi Barish¹, Kathryn Berg¹, Jeffrey Drozd²

¹Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.

Development (Cambridge, England)

|December 1, 2023

概括

基因组H2B单双化 (H2Bub1) 对心脏发育和心肌细胞分化至关重要. 适当的H2Bub1分布确保了组织特异性基因的正确表达,影响心脏发生.

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
心血管研究研究心血管研究

背景情况:

基因组H2B单双化 (H2Bub1) 的新变异与先天性心脏病有关.
H2Bub1在干细胞分化,乳毛功能,心肌细胞成熟和转录延长中发挥作用.
H2Bub1在心脏发生过程中的确切作用尚不清楚.

研究的目的:

研究H2Bub1及其沉积综合体在小鼠心脏发生和人类心肌细胞分化中的作用.
阐明H2Bub1分布如何影响心肌细胞发育期间的基因表达.

主要方法:

在人类诱导多能干细胞 (iPSC) 分化成心肌细胞过程中分析H2Bub1标记.
产生具有心脏特异性Rnf20缺失的小鼠,以评估其在心脏发生过程中的作用.
量化心脏特异性基因的全长转录在iPSC衍生的心肌细胞与改变的H2Bub1水平.

主要成果:

H2Bub1沉积复合体 (RNF20-RNF40-UBE2B) 对于小鼠心脏发生和人类iPSC-心肌细胞分化至关重要.
在小鼠中,心脏特异性的Rnf20缺失导致胚胎致死性和心肌异常.
在心肌细胞分化过程中,H2Bub1被动态调节,在关键的心脏特异性基因上保存,其减少会损害全长转录生成.

结论:

正常的H2Bub1分布对于适当的心脏发生和心肌细胞分化是不可或缺的.
H2Bub1调节组织特异性基因表达,可能通过促进全长转录的产生.

关键词:

心脏形态发生是心脏形态发生.一个心肌细胞.遗传性心脏病是一种先天性心脏病.表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

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