Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation.

ABSTRACT: The inability of adult human cardiomyocytes to proliferate is an obstacle to efficient cardiac regeneration after injury. Understanding the mechanisms that drive postnatal cardiomyocytes to switch to a non-regenerative state is therefore of great significance. Here we show that Arid1a, a subunit of the switching defective/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex, suppresses postnatal cardiomyocyte proliferation while enhancing maturation. Genome-wide transcriptome and epigenome analyses revealed that Arid1a is required for the activation of a cardiomyocyte maturation gene program by promoting DNA access to transcription factors that drive cardiomyocyte maturation. Furthermore, we show that ARID1A directly binds and inhibits the proliferation-promoting transcriptional c

SUBMITTER: Boogerd CJ 

PROVIDER: S-EPMC10404286 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature