Histone lysine methyltransferase SETD2 regulates coronary vascular development in embryonic mouse hearts

The focus of the manuscript is on the role of histone lysine methyltransferase SETD2, an H3K36me3 methyltransferase, in regulating embryonic cardiac development.In this study, we revealed that SETD2 is a crucial regulator of mouse heart development. Setd2 is highly expressed in embryonic stages and accounts for a predominant role of H3K36 trimethylation (H3K36me3) in embryonic mouse hearts. We also generated a mouse model with SETD2 deletion by Mesp1-Cre, and demonstrated that SETD2 and H3K36me3 are essential for coronary vascular growth and ventricular compaction. We also combined ChIP-seq and RNA-seq methods, and identified two cardiac-related genes downstream of SETD2 and H3K36me3: Rspo3 and Flrt2. Our results demonstrated that SETD2 modulates the H3K36me3 epigenetic landscape and is critical for coronary vascular formation and myocardium compaction in mice.