The Smyd Family of Methyltransferases: Role in Cardiac and Skeletal Muscle Physiology and Pathology.

Protein methylation plays a pivotal role in the regulation of various cellular processes including chromatin remodeling and gene expression. S ET and MY N D domain-containing proteins (Smyd) are a special class of lysine methyltransferases whose catalytic SET domain is split by an MYND domain. The hallmark feature of this family was thought to be the methylation of histone H3 (on lysine 4). However, several studies suggest that the role of the Smyd family is dynamic, targeting unique histone residues associated with both transcriptional activation and repression. Smyd proteins also methylate several non-histone proteins to regulate various cellular processes. Although we are only beginning to understand their specific molecular functions and role in chromatin remodeling, recent studies have advanced our understanding of this relatively uncharacterized family, highlighting their involvement in development, cell growth and differentiation and during disease in various animal models. This review summarizes our current knowledge of the structure, function and methylation targets of the Smyd family and provides a compilation of data emphasizing their prominent role in cardiac and skeletal muscle physiology and pathology.