Co-effects of m6A dynamics and chromatin accessibility changes regulate cardiomyocyte differentiation

The growth and differentiation of cardiomyocytes are primarily driven by gene expression dynamics, with various epigenetic modifications playing a crucial role in this process. One of the most common modifications on mRNA, m6A, influences the regulation of mRNA metabolism; however, its function remains enigmatic. In this study, we identified a correlation between m6A modification and cardiomyocyte differentiation by profiling m6A dynamics during the transition of pluripotent stem cells into cardiomyocytes. Although the overall m6A modification level remains relatively stable, most genes exhibit changes in their m6A levels as cardiomyocyte differentiation progresses. We observed that alterations in chromatin accessibility can impact the binding capabilities of m6A writers, erasers, and readers, consequently affecting m6A levels. Furthermore, the coordinated changes of m6A and chromatin accessibility are closely associated with early-stage cardiomyocyte differentiation. These findings suggest that m6A is a significant factor in determining the fate of cardiomyocyte differentiation, shedding light on its role in this critical process. Overall design: Comparative m6A profiling analysis of Pooling MeRIP-seq data for hESC, mesoderm, cardiac progenitor and cardiomyocytes.