Screening of histone modulators small molecule library reveals Kdm5b as a major epigenetic modulator of cell cycle gene expression in Cardiomyocyte
In this study, through a small molecule screening, we defined the histone lysine demethylase, Kdm5b, as a major epigenetic driver that controls the CM cell cycle gene expression in neonatal stage and can be reintroduced in adult CMs to induce cell cycle. Mechanistically, RNAseq and CUT&RUN analyses of Kdm5b KD in NMCM P1 revealed that Kdm5b modulates the expression and the enrichment of H3K4me3 methylation around the regulatory regions of the genes involved in cell cycle. Overall design: RNA sequencing profiling in postnatal P1 control Kdm5b FF mice heart and Kdm5b cardiac specific KO mice heart