Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development

查看全文 作　　者：Xianfa [1]Yang;Boqiang [2]Hu;Jiaoyang [1]Liao;Yunbo [3]Qiao;Yingying [1]Chen;Yun [1]Qian;Su [1]Feng;Fang [1]Yu;Ji [2]Dong;Yu [2]Hou;He [1]Xu;Ran [1]Wang;Guangdun [1,4,5,6]Peng;Jinsong [1,7]Li;Fucnou [2,8,9]Tang;Naihe [1,6,7]Jing

机构地区：[1]State Key Laboratory of Cell Biology,CAS Center for Excellencein Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,200031 Shanghai,China;[2]Beijing Advanced Innovation Center for Genomics,College of Life Sciences,Peking University,100871 Beijing,China;[3]Precise Genome Engineering Center,School of Life Sciences,Guangzhou University,Guangzhou 510006 Guangdong,China;[4]CAS Key Laboratory of RegenerativeBiology and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530 Guangdong,China;[5]Guangzhou Regenerative Medicine and Health Guangdong Laboratory(GRMH-GDL),Guangzhou 510005 Guangdong,China;[6]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,100101 Beijing,China;[7]School of Life Science and Technology,Shanghai Tech University,201210 Shanghai,China;[8]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation,100871 Beijing,China;[9]Peking-Tsinghua Center for Life Sciences,Peking University,100871Beijing,China

出　　处：《Cell Research》索引2019年第29卷第11期,共16页

基　　金：This work was supported in part by the National Key Basic Research and Development Program of China(2018YFA0800100,2018YFA0108000,2018YFAO107200,2017YFAO102700,2014CB964804,2018YFAO107601 and 2015CB964500);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020501 and XDA16020404);the Genome Tagging Project,and the National Natural Science Foundation of China(31900454,31501178,31430058,31571513,31630043,31871456,91519314,31661143042,81561138005,31625018,81521002,31530048,81672117 and 31730062);Shanghai Municipal Commission for Science and Technology(17JC1400900 and 17411954900). 摘　　要：Primary germ layers have the potential to form all tissues in the mature organism,and their formation during gastrulation requires precise epigenetic modulation of both proximal and distal regulatory elements.Previous studies indicated that spatial and temporal patterns of gene expression in the gastrula predispose individual regions to distinct cell fates.However,the underlying epigenetic mechanisms remain largely unexplored.Here,we profile the spatiotemporal landscape of the epigenome and transcriptome of the mouse gastrula.We reveal the asynchronous dynamics of proximal chromatin states during germ layer formation as well as unique gastrula-specific epigenomic features of regulatory elements,which have strong usage turnover dynamics and clear germ layerspecific signatures.Importantly,we also find that enhancers around organogenetic genes,which are weakly expressed at the gastrulation stage,are frequently pre-marked by histone H3 lysine 27 acetylation(H3K27ac)in the gastrula.By using the transgenic mice and genome editing system,we demonstrate that a pre-marked enhancer,which is located in the intron of a brain-specific gene 25W009E07Rik,exhibits specific enhancer activity in the ectoderm and future brain tissue,and also executes important function during mouse neural differentiation.Taken together,our study provides the comprehensive epigenetic information for embryonic patterning during mouse gastrulation,demonstrates the importance of gastrula pre-marked enhancers in regulating the correct development of the mouse embryo,and thus broadens the current understanding of mammalian embryonic development and related diseases. 关键词：signature landscape WEAKLY

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Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development

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