KMT2D regulates specific programs in heart development via histone H3 lysine 4 di-methylation.
Development
; 143(5): 810-21, 2016 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-26932671
ABSTRACT
KMT2D, which encodes a histone H3K4 methyltransferase, has been implicated in human congenital heart disease in the context of Kabuki syndrome. However, its role in heart development is not understood. Here, we demonstrate a requirement for KMT2D in cardiac precursors and cardiomyocytes during cardiogenesis in mice. Gene expression analysis revealed downregulation of ion transport and cell cycle genes, leading to altered calcium handling and cell cycle defects. We further determined that myocardial Kmt2d deletion led to decreased H3K4me1 and H3K4me2 at enhancers and promoters. Finally, we identified KMT2D-bound regions in cardiomyocytes, of which a subset was associated with decreased gene expression and decreased H3K4me2 in mutant hearts. This subset included genes related to ion transport, hypoxia-reoxygenation and cell cycle regulation, suggesting that KMT2D is important for these processes. Our findings indicate that KMT2D is essential for regulating cardiac gene expression during heart development primarily via H3K4 di-methylation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Histonas
/
Regulação da Expressão Gênica no Desenvolvimento
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Proteína de Leucina Linfoide-Mieloide
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Coração
/
Lisina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Development
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos