The transcriptional activator Klf5 recruits p300-mediated H3K27ac for maintaining trophoblast stem cell pluripotency  

作　　者：Chengli Dou Linhui Wu Jingjing Zhang Hainan He Tian Xu Zhisheng Yu Peng Su Xia Zhang Junling Wang Yi-Liang Miao Jilong Zhou 

机构地区：[1]Institute of Stem Cell and Regenerative Biology,College of Animal Science and Veterinary Medicine,Huazhong Agricultural University,Wuhan 430070,China [2]Key Laboratory of Agricultural Animal Genetics,Breeding and Reproduction(Huazhong Agricultural University),Ministry of Education,Wuhan 430070,China [3]Department of Reproductive Medicine,Huangshi Central Hospital,Affiliated Hospital of Hubei Polytechnic,Edong Healthcare Group,Huangshi 435000,China [4]Hubei Hongshan Laboratory,Wuhan 430070,China

出　　处：《Journal of Molecular Cell Biology》2023年第7期31-44,共14页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Natural.Science Foundation of China(31970822 and 31902161);the Key Research and Development Program of Hubei Province(2021BBA221 and 2022BCE002);the Fundamental Research Funds for the Central Universities(2662022DKPY001);the Major Project of Hubei Hongshan Laboratory(2021hszdo03)。

摘　　要：The effective proliferation and differentiation of trophoblast stem cells(TSCs)is indispensable for the development of the placenta,which is the key to maintaining normal fetal growth during pregnancy.Kruppel-like factor 5(Klf5)is implicated in the activation of pluripotency gene expression in embryonic stem cells(ESCs),yet its function in TSCs is poorly understood.Here,we showed that Klf5 knockdown resulted in the downregulation of core TSC-specific genes,consequently causing rapid differentiation of TSCs.Consistently,Klf5-depleted embryos lost the ability to establish TSCs in vitro.At the molecular level,Klf5 preferentially occupied the proximal promoter regions and maintained an open chromatin architecture of key TSC-specific genes.Deprivation of Klf5 impaired the enrichment of p300,a major histone acetyl transferase of H3 lysine 27 acetylation(H3K27ac),and further reduced the occupancy of H3K27ac at promoter regions,leading to decreased transcriptional activity of TSC pluripotency genes.Thus,our findings highlight a novel mechanism of Klf5 in regulating the self-renewal and differentiation of TSCs and provide a reference for understanding placental development and improving pregnancy rates.

关 键 词：Klf5 trophoblast stem cells SELF-RENEWAL chromatin accessibility P300 H3K27ac 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]