PUBLICATION

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

Authors
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.
ID
ZDB-PUB-180816-16
Date
2018
Source
PLoS Genetics   14: e1007578 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Humans
  • Gene Expression Regulation, Developmental
  • Embryonic Development/drug effects
  • Heart/drug effects
  • Heart/embryology
  • Transcriptome
  • Gene Expression Profiling
  • Disease Models, Animal
  • Mutation, Missense
  • Child, Preschool
  • Epigenesis, Genetic*
  • Heart Defects, Congenital/genetics
  • Histone Deacetylase 1/genetics
  • Histone Deacetylase 1/physiology
  • Histone Methyltransferases/genetics
  • Histone Methyltransferases/physiology*
  • Adolescent
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Infant
  • Histone-Lysine N-Methyltransferase/genetics
  • Histone-Lysine N-Methyltransferase/physiology*
  • Exome Sequencing
  • Male
  • Protein Conformation
  • Female
  • Cohort Studies
  • Animals
  • Child
  • Sequence Analysis, RNA
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • CRISPR-Cas Systems
(all 33)
PubMed
30110327 Full text @ PLoS Genet.
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*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.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Human Disease Fish Conditions Evidence
congenital heart diseaseTAS
congenital heart diseasesmyd4zf3020/zf3020; zf2036Tgstandard conditionsIC
1 - 2 of 2
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Sequence Targeting Reagents
Fish
Fish
smyd4zf3020/+; zf2036Tg
smyd4zf3020/zf3020; zf2036Tg
TU
1 - 3 of 3
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Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
1 - 1 of 1
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Mapping
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Citation
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:e1007578.