The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish.
PLoS Genet
; 14(8): e1007578, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-30110327
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
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Histona-Lisina N-Metiltransferase
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Proteínas de Peixe-Zebra
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Epigênese Genética
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Histona Metiltransferases
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Animals
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article