Speaker
Description
Differentiated cardiomyocytes (CMs) must undergo diverse morphological and functional changes during postnatal development. However, the initiation and coordination of these processes remain unclear. We reveal an integrated, time-ordered transcriptional network that begins with expression of genes for cell-cell connections and leads to a sequence of structural, cell cycle, functional, and metabolic transitions in mouse postnatal hearts. Depletion of histone H2B ubiquitin ligase RNF20 disrupts this gene network and CM polarization. Using ATAC-Seq analysis, we demonstrated that RNF20 contributes to chromatin accessibility. As such, RNF20 is likely to facilitate the binding of transcription factors at the promoters of genes involved in cell-cell connections and actin organization, crucial for CM polarization and functional integration. These results suggest that CM polarization is one of the earliest events during postnatal heart development, and our findings highlight a previously unrecognized role for RNF20 in regulating CM polarity and the transition of postnatal gene program.
