Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish

Chenglu Xiao, Lu Gao, Yu Hou, Congfei Xu, Nannan Chang, Fang Wang, Keping Hu, Aibin He, Ying Luo, Jun Wang, Jinrong Peng, Fuchou Tang, Xiaojun Zhu () and Jing-Wei Xiong ()
Additional contact information
Chenglu Xiao: Institute of Molecular Medicine, Peking University
Lu Gao: Institute of Molecular Medicine, Peking University
Yu Hou: Biodynamic Optical Imaging Center, Peking University
Congfei Xu: School of Life Sciences, University of Science and Technology of China
Nannan Chang: Institute of Molecular Medicine, Peking University
Fang Wang: College of Engineering, Peking University
Keping Hu: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences
Aibin He: Institute of Molecular Medicine, Peking University
Ying Luo: College of Engineering, Peking University
Jun Wang: School of Life Sciences, University of Science and Technology of China
Jinrong Peng: College of Animal Sciences, Zhejiang University
Fuchou Tang: Biodynamic Optical Imaging Center, Peking University
Xiaojun Zhu: Institute of Molecular Medicine, Peking University
Jing-Wei Xiong: Institute of Molecular Medicine, Peking University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract 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.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms13787 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13787

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13787

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().