Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome

Dilek Colak, Nikica Zaninovic, Michael S. Cohen, Zev Rosenwaks, Wang Yong Yang, Jeannine Gerhardt, Matthew D. Disney, Samie R. Jaffrey

Research output: Contribution to journalArticlepeer-review

227 Scopus citations


Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide-repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5′ untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA.

Original languageEnglish (US)
Pages (from-to)1002-1005
Number of pages4
Issue number6174
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • General


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