Details
- Autor(en) / Beteiligte
- Titel
- The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish
- Ist Teil von
- PLoS genetics, 2018-08, Vol.14 (8), p.e1007578
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7404, 1553-7390eISSN: 1553-7404DOI: 10.1371/journal.pgen.1007578Titel-ID: cdi_plos_journals_2250665542
- Format
- –
- Schlagworte
- Acetylation, Adolescent, Alzheimers disease, Analysis, Animals, Biochemistry, Bioinformatics, Biology and Life Sciences, Birth defects, Cardiovascular disease, Child, Child, Preschool, Cohort Studies, Collaboration, Congenital diseases, CRISPR, CRISPR-Cas Systems, CRISPR-Cas technology, Danio rerio, Disease Models, Animal, Education, Embryonic Development - drug effects, Endoplasmic reticulum, Epigenesis, Genetic, Epigenetics, Female, Funding, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Developmental, Genetic aspects, Genetic diversity, Genetic regulation, Genetic variance, Genetics, Health aspects, Heart, Heart - drug effects, Heart - embryology, Heart Defects, Congenital - genetics, Histone Deacetylase 1 - genetics, Histone Deacetylase 1 - physiology, Histone methyltransferase, Histone-Lysine N-Methyltransferase - genetics, Histone-Lysine N-Methyltransferase - physiology, Hospitals, Humans, Infant, Laboratories, Lysine, Male, Medicine, Medicine and Health Sciences, Metabolic pathways, Metabolism, Molecular biology, Morphogenesis, Mutation, Mutation, Missense, Pediatrics, Physiological aspects, Protein Conformation, Proteins, Research and Analysis Methods, Sequence Analysis, RNA, Software, Supervision, Transcriptome, Whole Exome Sequencing, Zebra fish, Zebrafish, Zebrafish - embryology, Zebrafish - genetics, Zebrafish Proteins - genetics, Zebrafish Proteins - physiology