Epigenetic mechanism of FMR1 inactivation in Fragile X syndrome.
Int J Dev Biol
; 61(3-4-5): 285-292, 2017.
Article
em En
| MEDLINE
| ID: mdl-28621425
ABSTRACT
Fragile X syndrome is the most frequent cause of inherited intellectual disability. The primary molecular defect in this disease is the expansion of a CGG repeat in the 5' region of the fragile X mental retardation1 (FMR1) gene, leading to de novo methylation of the promoter and inactivation of this otherwise normal gene, but little is known about how these epigenetic changes occur during development. In order to gain insight into the nature of this process, we have used cell fusion technology to recapitulate the events that occur during early embryogenesis. These experiments suggest that the naturally occurring Fragile XFMR1 5' region undergoes inactivation post implantation in a Dicer/Ago-dependent targeted process which involves local SUV39H-mediated tri-methylation of histone H3K9. It thus appears that Fragile X syndrome may come about through inadvertent siRNA-mediated heterochromatinization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica no Desenvolvimento
/
Metilação de DNA
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Epigênese Genética
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Proteína do X Frágil da Deficiência Intelectual
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Síndrome do Cromossomo X Frágil
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Dev Biol
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article