Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate

查看全文 作　　者：Rui [1,2,3]Gao;Xingqun [4]Liang;Sirisha [1]Cheedipudi;Julio [1,2,3]Cordero;Xue [4]Jiang;Qingquan [4]Zhang;Luca [1]Caputo;Stefan [1]Günther;Carsten [1]Kuenne;Yonggang [1,2,3]Ren;Shoumo [5]Bhattacharya;Xuejun [1]Yuan;Guillermo [1]Barreto;Yihan [4]Chen;Thomas [1]Braun;Sylvia M. [6]Evans;Yunfu [4]Sun;Gergana [1,2,3,7]Dobreva

机构地区：[1]Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany;[2]Department of Anatomy and Developmental Biology, CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;[3]European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;[4]Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai 200120, China;[5]Department of Cardiovascular Medicine, University of Oxford,Oxford, UK;[6]Department of Medicine, Skaggs School of Pharmacy, University of California, San Diego, La Jolla, CA 92093, USA;[7]Medical Faculty, University of Frankfurt, 60590 Frankfurt am Main, Germany

出　　处：《Cell Research》索引2019年第29卷第6期,共16页

基　　金：the LOEWE Center for Cell and Gene Therapy (CGT), financed by the Hessian Ministry of Higher Education, Research and Arts (III L 4- 518/17.004 (2013);the SFB TRR 81, the SFB 873, the SFB 1213, the SFB 1366 funded by the DFG and the AngioFormatics grant financed by the state of Baden-Wurttemberg;YFS was supported by grants from the Ministry of Science and Technology China (2013CB967400) and National Natural Science Foundation of China (NSFC)(81570285);S.M.E. by grants from NIH (HL123747, HL119967) and X.Q.L. by grants from NSFC (81370196, 81670448);X.Y.and T.B. by the SFB 1213. 摘　　要：Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and differentiation steps. Here we show that Isl1 acts as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which shows congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, we uncover a regulatory network downstream of Isl1 that orchestrates cardiogenesis. Mechanistically, we show that Isl1 binds to compacted chromatin and works in concert with the Brg1-Baf60c-based SWI/SNF complex to promote permissive cardiac lineage-specific alterations in the chromatin landscape not only of genes with critical functions in cardiac progenitor cells, but also of cardiomyocyte structural genes that are highly expressed when Isl1 itself is no longer present. Thus, the Isl1/Brg1-Baf60c complex plays a crucial role in orchestrating proper cardiogenesis and in establishing epigenetic memory of cardiomyocyte fate commitment. 关键词：CELL totipotent COMMITMENT

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Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate

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