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

Author

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  • Chenglu Xiao

    (Institute of Molecular Medicine, Peking University
    Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University
    State Key Laboratory of Natural and Biomimetic Drugs)

  • Lu Gao

    (Institute of Molecular Medicine, Peking University
    Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University
    State Key Laboratory of Natural and Biomimetic Drugs)

  • Yu Hou

    (Biodynamic Optical Imaging Center, Peking University
    College of Life Sciences, Peking University)

  • Congfei Xu

    (School of Life Sciences, University of Science and Technology of China
    Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China)

  • Nannan Chang

    (Institute of Molecular Medicine, Peking University
    Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University
    State Key Laboratory of Natural and Biomimetic Drugs)

  • Fang Wang

    (College of Engineering, Peking University)

  • Keping Hu

    (Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Aibin He

    (Institute of Molecular Medicine, Peking University
    Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University)

  • Ying Luo

    (College of Engineering, Peking University)

  • Jun Wang

    (School of Life Sciences, University of Science and Technology of China
    Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China)

  • Jinrong Peng

    (College of Animal Sciences, Zhejiang University)

  • Fuchou Tang

    (Biodynamic Optical Imaging Center, Peking University
    College of Life Sciences, Peking University)

  • Xiaojun Zhu

    (Institute of Molecular Medicine, Peking University
    Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University
    State Key Laboratory of Natural and Biomimetic Drugs)

  • Jing-Wei Xiong

    (Institute of Molecular Medicine, Peking University
    Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University
    State Key Laboratory of Natural and Biomimetic Drugs)

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.

Suggested Citation

  • 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 & Jing-Wei Xiong, 2016. "Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13787
    DOI: 10.1038/ncomms13787
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    Cited by:

    1. Xiaohai Zhou & Chenyang Zhang & Xueying Wu & Xinli Hu & Yan Zhang & Xuelian Wang & Lixia Zheng & Peng Gao & Jianyong Du & Wen Zheng & Haibao Shang & Keping Hu & Zhengfan Jiang & Yu Nie & Shengshou Hu , 2022. "Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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