The Roles of Histone Lysine Methyltransferases in Heart Development and Disease

Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue patterning, and in regulating cellular metabolic processes. It has also been associated with varying human developmental disorders. Heart disease has been linked to deregulated histone lysine methylation, and lysine-specific methyltransferases (KMTs) are overrepresented, i.e., more numerous than expected by chance, among the genes with variants associated with congenital heart disease. This review outlines the available evidence to support a role for individual KMTs in heart development and/or disease, including genetic associations in patients and supporting cell culture and animal model studies. It concludes with new advances in the field and new opportunities for treatment.

Automated summary

Epigenetic marks, such as lysine-specific histone methylation, play crucial roles in development by regulating the structure of the genome. Dysregulation of histone lysine methylation has been associated with heart disease, and genes involved in this process are overrepresented in congenital heart disease. This review summarizes the evidence supporting the role of specific lysine-specific methyltransferases in heart development and disease, including genetic associations and animal studies, and discusses new opportunities for treatment.