TY  - JOUR
TI  - Epigenetic mechanism of FMR1 inactivation in Fragile X syndrome
AU  - Hecht, Merav
AU  - Tabib, Amalia
AU  - Kahan, Tamar
AU  - Orlanski, Shari
AU  - Gropp, Michal
AU  - Tabach, Yuval
AU  - Yanuka, Ofra
AU  - Benvenisty, Nissim
AU  - Keshet, Ilana
AU  - Cedar, Howard
T2  - The International Journal of Developmental Biology
AB  - 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.
PY  - 2017
DO  - 10.1387/ijdb.170022hc
VL  - 61
IS  - 3-4-5
SP  - 285
EP  - 292
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/170022hc
Y2  - 2024/04/28/19:36:26
ER  -