Reactivation of FMR1 by CRISPR/Cas9-Mediated Deletion of the Expanded CGG-Repeat of the Fragile X Chromosome.
PLoS One
; 11(10): e0165499, 2016.
Article
em En
| MEDLINE
| ID: mdl-27768763
ABSTRACT
Fragile X syndrome (FXS) is a common cause of intellectual disability that is most often due to a CGG-repeat expansion mutation in the FMR1 gene that triggers epigenetic gene silencing. Epigenetic modifying drugs can only transiently and modestly induce FMR1 reactivation in the presence of the elongated CGG repeat. As a proof-of-principle, we excised the expanded CGG-repeat in both somatic cell hybrids containing the human fragile X chromosome and human FXS iPS cells using the CRISPR/Cas9 genome editing. We observed transcriptional reactivation in approximately 67% of the CRISPR cut hybrid colonies and in 20% of isolated human FXS iPSC colonies. The reactivated cells produced FMRP and exhibited a decline in DNA methylation at the FMR1 locus. These data demonstrate the excision of the expanded CGG-repeat from the fragile X chromosome can result in FMR1 reactivation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Deleção de Sequência
/
Repetições de Trinucleotídeos
/
Proteína do X Frágil da Deficiência Intelectual
/
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
/
Síndrome do Cromossomo X Frágil
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos