Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration

4Citations
Citations of this article
11Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.

Cite

CITATION STYLE

APA

Xiao, C., Hou, J., Wang, F., Song, Y., Zheng, J., Luo, L., … Xiong, J. W. (2023). Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration. Npj Regenerative Medicine, 8(1). https://doi.org/10.1038/s41536-023-00293-4

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free