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Epigenetic mechanism of FMR1 inactivation in Fragile X syndrome

Item Type:Article
Title:Epigenetic mechanism of FMR1 inactivation in Fragile X syndrome
Creators Name:Hecht, M. and Tabib, A. and Kahan, T. and Orlanski, S. and Gropp, M. and Tabach, Y. and Yanuka, O. and Benvenisty, N. and Keshet, I. and Cedar, H.
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.
Keywords:DNA Methylation, Chromatin, RNAi, Histone Modification, Animals, Mice
Source:International Journal of Developmental Biology
Publisher:University of the Basque Country Press
Page Range:285-292
Official Publication:https://doi.org/10.1387/ijdb.170022hc
PubMed:View item in PubMed

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