Smyd3 Is Required for the Development of Cardiac and Skeletal Muscle in Zebrafish

Abstract

Modifications of histone tails are involved in the regulation of a wide range of biological processes including cell cycle, cell survival, cell division, and cell differentiation. Among the modifications, histone methylation plays a critical role in cardiac and skeletal muscle differentiation. In our earlier studies, we found that SMYD3 has methyltransferase activity to histone H3 lysine 4, and that its up-regulation is involved in the tumorigenesis of human colon, liver, and breast. To clarify the role of Smyd3 in development, we have studied its expression patterns in zebrafish embryos and the effect of its suppression on development using Smyd3-specific antisense morpholino-oligonucleotides. We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle.

Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization

“…In this context, the formation of complexes around lysine methylation at the titin filament could be viewed as functionally analogous to the formation of complexes around lysine methylation at the chromatin fiber. In vertebrates, several Smyd family KMTases are expressed most highly in muscle cells (Gottlieb et al 2002;Fujii et al 2003;Tan et al 2006;Kawamura et al 2008;Sun et al 2008;Thompson and Travers 2008). Thus, it is attractive to speculate that the Smyd family of KMTases will prove to support sarcomeric contractile function through methylation of various muscle proteins.…”

Zebrafish foxc1a Plays a Crucial Role in Early Somitogenesis by Restricting the Expression of aldh1a2 Directly

“…To investigate whether the somite differentiation was affected in foxc1a mutants at late somitogenesis, we examined the expressions of myod1 and three terminal differentiation makers for skeletal muscle (42,46), including mylpfa (marker gene for fast muscle), smyhc1 (maker gene for slow muscle), and ckma (maker gene for both slow and fast muscle), in the embryos at 24 hpf. It turned out that the foxc1a null embryos exhibited similar expression patterns of myod1 (Fig.…”

The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy

“…Given its function in regulating zebrafish skeletal myogenesis (Fujii et al 2011), we investigated the role of SMYD3 in a cell culture model of mammalian myogenesis. SMYD3 expression was reduced in C2C12 cells by transducing them with a specific shRNA.…”