Trim28 citrullination maintains mouse embryonic stem cell pluripotency via regulating Nanog and Klf4 transcription  

作　　者：Yaguang Zhang Xiaowen Wan Lei Qiu Lian Zhou Qing Huang Mingtian Wei Xueqin Liu Sicheng Liu Bo Zhang Junhong Han 

机构地区：[1]State Key Laboratory of Biotherapy and Cancer Center,National Clinical Research Center for Geriatrics,and Frontiers Science Center for Disease-related Molecular Network,West China Hospital,Sichuan University,Chengdu 610041,China [2]Department of Gastrointestinal Surgery,and Frontiers Science Center for Disease-related Molecular Network,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Science China(Life Sciences)》2023年第3期545-562,共18页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(31972884);the National Key Research and Development Program of China(2018YFC1312300);the National Clinical Research Center for Geriatrics(Z20201007);1·3·5 Project for Disciplines of Excellence,West China Hospital(ZYGD18003);the Postdoctoral Research Project,West China Hospital,Sichuan University(18HXBH068);the Natural Science Foundation of Sichuan,China(2022NSFSC1424)。

摘　　要：Protein citrullination,including histone H1 and H3 citrullination,is important for transcriptional regulation,DNA damage response,and pluripotency of embryonic stem cells(ESCs).Tripartite motif containing 28(Trim28),an embryonic development regulator involved in ESC self-renewal,has recently been identified as a novel substrate for citrullination by Padi4.However,the physiological functions of Trim28 citrullination and its role in regulating the chromatin structure and gene transcription of ESCs remain unknown.In this paper,we show that Trim28 is specifically citrullinated in mouse ESCs(m ESCs),and that the loss of Trim28 citrullination induces loss of pluripotency.Mechanistically,Trim28 citrullination enhances the interaction of Trim28with Smarcad1 and prevents chromatin condensation.Additionally,Trim28 citrullination regulates m ESC pluripotency by promoting transcription of Nanog and Klf4 which it does by increasing the enrichment of H3K27ac and H3K4me3 and decreasing the enrichment of H3K9me3 in the transcriptional regulatory region.Thus,our findings suggest that Trim28citrullination is the key for the epigenetic activation of pluripotency genes and pluripotency maintenance of ESCs.Together,these results uncover a role Trim28 citrullination plays in pluripotency regulation and provide novel insight into how citrullination of proteins other than histones regulates chromatin compaction.

关 键 词：CITRULLINATION CHROMATIN embryonic stem cell PLURIPOTENCY Trim28 

分 类 号：Q942[生物学—植物学]