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Bend family proteins mark chromatin boundaries and synergistically promote early germ cell differentiation

查看全文 作  者:Guang [1,2]Shi;Yaofu [1,2]Bai;Xiya [1,6]Zhang;Junfeng [1]Su;Junjie [1]Pang;Quanyuan [1]He;Pengguihang [3]Zeng;Junjun [3]Ding;Yuanyan [1]Xiong;Jingran [1,2]Zhang;Jingwen [1,2]Wang;Dan [4]Liu;Wenbin [1,2]Ma;Junjiu [1]Huang;Zhou [1,2,5]Songyang 高影响力作者 机构地区:[1]MOE Key Laboratory of Gene Function and Regulation,Guangzhou Key Laboratory of Healthy Aging Research,School of Life Sciences,Sun Yat-sen University,Guangzhou 510275,China;[2]Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;[3]Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China;[4]Verna and Marrs Mclean Department of Biochemistry and Molecular Biology,Baylor College of Medicine,One Baylor Plaza,Houston,TX 77030,USA;[5]Bioland Laboratory,Guangzhou 510320,China;[6]Center for Reproductive Medicine,The Third Affiliated Hospital of Sun Yat-sen University,Sun Yat-sen University,Guangzhou 510630,China高影响力机构 出  处:《Protein & Cell》索引2022年第13卷第10期,共21页高影响力期刊 基  金:the National Key R&D Program of China(2017YFA0102801);The National Natural Science Foundation of China(Grant Nos.31930058,31671540,32170802,and 31301082);Natural Science Foundation of Guangdong Province(2015B020228002,2017A030313093);Guangdong Basic and Applied Basic Research Foundation(2019A1515011422,2021A1515010759). 摘  要:Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro.In this study,we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation(BiFC)platform for protein-protein interaction screens and epiblast-like cell(EpiLC)-induction assays using reporter mouse embryonic stem cells(mESCs).Investigation of candidate interaction partners of core human pluripotent factors OCT4,NANOG,KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell(PGC)-inducing factors including BEN-domain(BEND/Bend)family members.Through RNA-seq,ChIP-seq,and ATAC-seq analyses,we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro.Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development. 关 键 词:embryonic stem cell self-renewal and differentiation early development chromatin organization Bend5 and Bend4
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