While increasing evidence indicates the important function of histone 
methylation during development, how this process influences cardiac development 
in vertebrates has not been explored. Here, we elucidate the functions of two 
histone H3 lysine 4 (H3K4) methylation enzymes, SMYD3 and SETD7, during 
zebrafish heart morphogenesis using gene expression profiling by whole mount in 
situ hybridization and antisense morpholino oligonucleotide (MO)-based gene 
knockdown. We find both smyd3 and setd7 are highly expressed within developing 
zebrafish heart and knock-down of these genes led to severe defects in cardiac 
morphogenesis without altering the expressions pattern of heart markers, 
including cmlc2, vmhc, and amhc. Furthermore, double knock-down by coinjection 
of smyd3 and setd7 MOs caused the synergistic defects in heart development. As 
similar to knock-down effect, overexpression of these genes also caused the 
heart morphogenesis defect in zebrafish. These results indicate that histone 
modifying enzymes, SMYD3 and SETD7, appear to function synergistically during 
heart development and their proper functioning is essential for normal heart 
morphogenesis during development.