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
-
- Transcriptome
- Adolescent
- Exome Sequencing
- Child, Preschool
- Histone Methyltransferases/genetics
- Histone Methyltransferases/physiology*
- Sequence Analysis, RNA
- Gene Expression Profiling
- Protein Conformation
- Histone-Lysine N-Methyltransferase/genetics
- Histone-Lysine N-Methyltransferase/physiology*
- Epigenesis, Genetic*
- Humans
- Child
- Heart Defects, Congenital/genetics
- Histone Deacetylase 1/genetics
- Histone Deacetylase 1/physiology
- Mutation, Missense
- Heart/drug effects
- Heart/embryology
- Male
- Embryonic Development/drug effects
- CRISPR-Cas Systems
- Disease Models, Animal
- Animals
- Infant
- Zebrafish/embryology
- Zebrafish/genetics*
- Female
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- Gene Expression Regulation, Developmental
- Cohort Studies
- PubMed
- 30110327 Full text @ PLoS Genet.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping