[Chromatin changes caused by CGG repeat expansion in fmr1 gene]

Fragile X syndrome is inheritable neurodegenerative disease with frequency 1/4000-1/6000. It is the main cause of inheritable mental retardation. Progression of the disorder is caused by CGG repeat expansion in 5' UTR of fmr1 (fragile X mental retardation 1) gene. Normal allele contains ≤ 54 repeats. Allele containing 55-200 repeats induce fragile X-associated disorders: fragile X-associated tremor/ataxia syndrome and fragile-X associated primary ovarian insufficiency. Allele containing ≥ 200 repeats induce fragile X syndrome. Absence of FMRP protein is the main reason for the syndrome progression. FMRP is RNA-binding protein responsible for neuronal differentiation. In case of increasing CGG triplets number the expression of fmr1 gene is repressed. Results of CGG expansion are DNA methylation, histone methylation and deacetylation. Repression transcription factors bind such chromatin and lead to disorder progression. In this review we discuss the mechanisms of heterochromatinization induced by CGG repeat expansion in the promoter region of fmr1 gene.