干细胞
同源盒蛋白纳米
染色质
重编程
组蛋白甲基化
组蛋白H3
癌症研究
细胞分化
组蛋白H2A
作者
Yi Fang,Xiaojiang Xu,Jun Ding,Lu Yang,Mary T. Doan,Peer W. F. Karmaus,Nathaniel W. Snyder,Yingming Zhao,Jian-Liang Li,Xiaoling Li
标识
DOI:10.1016/j.stem.2020.12.009
摘要
Summary Histone crotonylation is a non-acetyl histone lysine modification that is as widespread as acetylation. However, physiological functions associated with histone crotonylation remain almost completely unknown. Here we report that histone crotonylation is crucial for endoderm differentiation. We demonstrate that key crotonyl-coenzyme A (CoA)-producing enzymes are specifically induced in endodermal cells during differentiation of human embryonic stem cells (hESCs) in vitro and in mouse embryos, where they function to increase histone crotonylation and enhance endodermal gene expression. Chemical enhancement of histone crotonylation promotes endoderm differentiation of hESCs, whereas deletion of crotonyl-CoA-producing enzymes reduces histone crotonylation and impairs meso/endoderm differentiation in vitro and in vivo. Our study uncovers a histone crotonylation-mediated mechanism that promotes endodermal commitment of pluripotent stem cells, which may have important implications for therapeutic strategies against a number of human diseases.
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