Fig. 3

Expanded FMR1 mRNA silences the FMR1 locus through an epigenetic mechanism. The FMR1 locus features a CGG trinucleotide repeat in the 5′UTR of the gene. Typically, the trinucleotide is repeated 5–40 times; however, expansion of this site to >200 repeats causes Fragile X syndrome. The trinucleotide repeat in the resulting expanded FMR1 mRNA transcript (1) binds to its CGG expansion at the DNA locus to form a heteroduplex. Through an unknown mechanism, this interaction silences transcription from the FMR1 locus (2). The locus then acquires a repressive chromatin state. Specifically, active histone marks H3K9ac and H3K4me2 are removed, while repressive mCG and H3K9me2 marks are added (3)