Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish | |
Xiao, Chenglu ; Gao, Lu ; Hou, Yu ; Xu, Congfei ; Chang, Nannan ; Wang, Fang ; Hu, Keping ; He, Aibin ; Luo, Ying ; Wang, Jun ; Peng, Jinrong ; Tang, Fuchou ; Zhu, Xiaojun ; Xiong, Jing-Wei | |
刊名 | NATURE COMMUNICATIONS |
2016 | |
关键词 | PEG-PLA NANOPARTICLES HEART REGENERATION NEURAL DEVELOPMENT CARDIOMYOCYTE PROLIFERATION CARDIAC REGENERATION CELL-DEVELOPMENT COMPLEXES TRANSCRIPTION EXPRESSION MOUSE |
DOI | 10.1038/ncomms13787 |
英文摘要 | The zebrafish possesses a remarkable capacity of adult heart regeneration, but the underlying mechanisms are not well understood. Here we report that chromatin remodelling factor Brg1 is essential for adult heart regeneration. Brg1 mRNA and protein are induced during heart regeneration. Transgenic over-expression of dominant-negative Xenopus Brg1 inhibits the formation of BrdU(+)/Mef2C(+) and Tg(gata4: EGFP) cardiomyocytes, leading to severe cardiac fibrosis and compromised myocardial regeneration. RNA-seq and RNAscope analyses reveal that inhibition of Brg1 increases the expression of cyclin-dependent kinase inhibitors such as cdkn1a and cdkn1c in the myocardium after ventricular resection; and accordingly, myocardial-specific expression of dn-xBrg1 blunts myocardial proliferation and regeneration. Mechanistically, injury-induced Brg1, via its interaction with Dnmt3ab, suppresses the expression of cdkn1c by increasing the methylation level of CpG sites at the cdkn1c promoter. Taken together, our results suggest that Brg1 promotes heart regeneration by repressing cyclin-dependent kinase inhibitors partly through Dnmt3ab-dependent DNA methylation.; National Basic Research Program of China [2012CB944501, 2010CB529503]; National Natural Science Foundation of China [31430059, 81470399, 31521062, 31271549, 81270164]; AstraZeneca Innovation Center China; SCI(E); ARTICLE; zhuxiaojun@pku.edu.cn; jingwei_xiong@pku.edu.cn; 7 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/458092] |
专题 | 生命科学学院 工学院 |
推荐引用方式 GB/T 7714 | Xiao, Chenglu,Gao, Lu,Hou, Yu,et al. Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish[J]. NATURE COMMUNICATIONS,2016. |
APA | Xiao, Chenglu.,Gao, Lu.,Hou, Yu.,Xu, Congfei.,Chang, Nannan.,...&Xiong, Jing-Wei.(2016).Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish.NATURE COMMUNICATIONS. |
MLA | Xiao, Chenglu,et al."Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish".NATURE COMMUNICATIONS (2016). |
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