PUBLICATION

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

Authors
Xiao, C., Gao, L., Hou, Y., Xu, C., Chang, N., Wang, F., Hu, K., He, A., Luo, Y., Wang, J., Peng, J., Tang, F., Zhu, X., Xiong, J.W.
ID
ZDB-PUB-161209-2
Date
2016
Source
Nature communications   7: 13787 (Journal)
Registered Authors
Peng, Jinrong, Wang, Fang, Xiong, Jing-Wei
Keywords
Cell proliferation, Chromatin remodelling, Development, Regeneration
Datasets
GEO:GSE81627
MeSH Terms
  • Cyclin-Dependent Kinase Inhibitor p57/metabolism
  • Zebrafish Proteins/physiology*
  • Regeneration
  • Adaptor Proteins, Signal Transducing/physiology*
  • Animals, Genetically Modified
  • Up-Regulation
  • Animals
  • Cell Proliferation
  • Zebrafish
  • DNA Methylation
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Heart/physiology*
(all 13)
PubMed
27929112 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
Figure Gallery (19 images) / 2
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ae1TgTransgenic Insertion
    hkz04tTgTransgenic Insertion
      pku328TgTransgenic Insertion
        pku362TgTransgenic Insertion
          pku363TgTransgenic Insertion
            pku364TgTransgenic Insertion
              pku365TgTransgenic Insertion
                ubs1TgTransgenic Insertion
                  1 - 8 of 8
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Fish
                  Antibodies
                  Orthology
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  CreEFGCre
                  DsRedEFGDsRed
                  EGFPEFGEGFP
                  GFPEFGGFP
                  1 - 4 of 4
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                  Mapping
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                  Citation
                  Xiao, C., Gao, L., Hou, Y., Xu, C., Chang, N., Wang, F., Hu, K., He, A., Luo, Y., Wang, J., Peng, J., Tang, F., Zhu, X., Xiong, J.W. (2016) Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish. Nature communications. 7:13787.