Open AccessEpigenetic mechanism of FMR1 inactivation in Fragile X syndrome
Author(s) -
Merav Hecht,
Amalia Tabib,
Tamar Kahan,
Shari Orlanski,
Michal Gropp,
Yuval Tabach,
Ofra Yanuka,
Nissim Benvenisty,
Ilana Keshet,
Howard Cedar
Publication year - 2017
Publication title -
the international journal of developmental biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.837
H-Index - 103
eISSN - 1696-3547
pISSN - 0214-6282
DOI - 10.1387/ijdb.170022hc
Subject(s) - biology , fragile x syndrome , epigenetics , fmr1 , genetics , chromosomal fragile site , dicer , dna methylation , histone , chromatin , methylation , gene , microbiology and biotechnology , fragile x , gene expression , rna interference , rna , chromosome
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.