| First Author | Xiao D | Year | 2018 |
| Journal | PLoS Genet | Volume | 14 |
| Issue | 8 | Pages | e1007578 |
| PubMed ID | 30110327 | Mgi Jnum | J:306888 |
| Mgi Id | MGI:6198406 | Doi | 10.1371/journal.pgen.1007578 |
| Citation | Xiao D, et al. (2018) The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish. PLoS Genet 14(8):e1007578 |
| abstractText | SMYD4 belongs to a family of lysine methyltransferases. We analyzed the role of smyd4 in zebrafish development by generating a smyd4 mutant zebrafish line (smyd4L544Efs*1) using the CRISPR/Cas9 technology. The maternal and zygotic smyd4L544Efs*1 mutants demonstrated severe cardiac malformations, including defects in left-right patterning and looping and hypoplastic ventricles, suggesting that smyd4 was critical for heart development. Importantly, we identified two rare SMYD4 genetic variants in a 208-patient cohort with congenital heart defects. Both biochemical and functional analyses indicated that SMYD4(G345D) was pathogenic. Our data suggested that smyd4 functions as a histone methyltransferase and, by interacting with HDAC1, also serves as a potential modulator for histone acetylation. Transcriptome and bioinformatics analyses of smyd4L544Efs*1 and wild-type developing hearts suggested that smyd4 is a key epigenetic regulator involved in regulating endoplasmic reticulum-mediated protein processing and several important metabolic pathways in developing zebrafish hearts. |
