Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation.
Stem Cell Reports
; 8(2): 290-304, 2017 02 14.
Article
em En
| MEDLINE
| ID: mdl-28111280
ABSTRACT
Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regulation during myocardial differentiation. Persistent nicotine exposure selectively inhibited expression of two cardiac genes, Tbx5 and Gata4, by promoter DNA hypermethylation. The nicotine-induced suppression on cardiac differentiation was restored by general nicotinic acetylcholine receptor inhibition. Consistent results of Tbx5 and Gata4 gene suppression and cardiac function impairment with decreased left ventricular ejection fraction were obtained from in vivo studies in offspring. Our results present a direct repressive effect of nicotine on myocardial differentiation by regulating cardiac gene suppression via promoter DNA hypermethylation, contributing to the etiology of smoking-associated cardiac defects.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Regulação da Expressão Gênica
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Metilação de DNA
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Proteínas com Domínio T
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Células Musculares
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Fator de Transcrição GATA4
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Nicotina
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2017
Tipo de documento:
Article