The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish

Deyong Xiao, Huijun Wang, Lili Hao, Xiao Guo, Xiaojing Ma, Yanyan Qian, Hongbo Chen, Jing Ma, Jin Zhang, Wei Sheng, Weinian Shou, Guoying Huang, Duan Ma

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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*1mutants 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*1and 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.

Original languageEnglish (US)
Article numbere1007578
JournalPLoS Genetics
Volume14
Issue number8
DOIs
StatePublished - Aug 2018

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Xiao, D., Wang, H., Hao, L., Guo, X., Ma, X., Qian, Y., Chen, H., Ma, J., Zhang, J., Sheng, W., Shou, W., Huang, G., & Ma, D. (2018). The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish. PLoS Genetics, 14(8), [e1007578]. https://doi.org/10.1371/journal.pgen.1007578