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
-
- Zebrafish
- Zebrafish Proteins/physiology*
- Animals, Genetically Modified
- Cyclin-Dependent Kinase Inhibitor p57/metabolism
- Regeneration
- Animals
- Myocardium/cytology
- Myocardium/metabolism*
- Heart/physiology*
- Up-Regulation
- Adaptor Proteins, Signal Transducing/physiology*
- DNA Methylation
- Cell Proliferation
- PubMed
- 27929112 Full text @ Nat. Commun.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping