Vol 49(2015) N 2 p. 179-184; DOI 10.1134/S0026893315010197
D.V. Yudkin1,2*, N.A. Lemskaya1, I.V. Grischenko2, A.A. Dolskiy2
Chromatin changes caused by expansion of CGG repeats in fmr1 gene1Institute of Molecular and Cellular Biology, Siberian Branch, Russian Academy of Science, Novosibirsk, 630090 Russia
2Novosibirsk State University, Novosibirsk, 630090 Russia
Received - 2014-07-14; Accepted - 2014-08-12
Fragile X syndrome is an inherited neurodegenerative disease with a frequency of 1/4000 -1/6000. It is the main cause of inheritable mental retardation. The progression of the disorder is caused by CGG repeat expansion in 5' UTR of fmr1 (fragile X mental retardation 1) gene. The normal allele contains 54 repeats. Alleles containing 55-200 repeats induce fragile X-associated disorders: fragile X-associated tremor/ataxia syndrome and fragile-X associated primary ovarian insufficiency. Alleles containing 200 repeats induce fragile X syndrome. The absence of FMRP protein is the main reason for the progression of the syndrome. 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 this chromatin and lead to the progression of the disorder. In this review, we discuss how heterochromatinization is induced by CGG repeat expansion in the promoter region of fmr1 gene.
fragile X syndrome, heterochromatinization, transcription, expression, methylation, acetylation, histones, tremor/ataxia syndrome, primary ovarian insufficiency