A cardiac transcriptional enhancer is repurposed during regeneration to activate an anti-proliferative program.

ABSTRACT: Zebrafish have a high capacity to regenerate their hearts. Several studies have surveyed transcriptional enhancers to understand how gene expression is controlled during heart regeneration. We have identified REN (the runx1 enhancer) that, during regeneration, regulates the expression of the nearby runx1 gene. We show that runx1 mRNA is reduced with deletion of REN (ΔREN), and cardiomyocyte proliferation is enhanced in ΔREN mutants only during regeneration. Interestingly, in uninjured hearts, ΔREN mutants have reduced expression of adamts1, a nearby gene that encodes a Collagen protease. This results in excess Collagen within cardiac valves of uninjured hearts. The ΔREN Collagen phenotype is rescued by an allele with Δrunx1 mutations, suggesting that in uninjured hearts REN regulates adamt

SUBMITTER: Rao A 

PROVIDER: S-EPMC11883283 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature