Chromatin Remodeling in the Noncoding Repeat Expansion Diseases

Daman Kumari,Karen Usdin

doi:10.1074/jbc.r800026200

Abstract

Friedreich ataxia, myotonic dystrophy type 1 and 3 forms of intellectual disability, fragile X syndrome, FRAXE mental retardation, and FRA12A mental retardation are repeat expansion diseases caused by expansion of CTG.CAG, GAA.TTC, or CGG.CCG repeat tracts. These repeats are transcribed but not translated. They are located in different parts of different genes and cause symptoms that range from ataxia and hypertrophic cardiomyopathy to muscle wasting, male infertility, and mental retardation, yet recent reports suggest that, despite these differences, the repeats may share a common property, namely the ability to initiate repeat-mediated epigenetic changes that result in heterochromatin formation.

Highlights

Chromatin Remodeling in the Noncoding Repeat Expansion Diseases*Daman Kumari and Karen Usdin From the Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830
The repeat expansion diseases arise from the expansion or increase in the number of repeats in a specific tandem repeat array
Other diseases like FXS, FRAXE MR, FRA12A MR, FRDA, and DM1 are caused by expansion of repeats that are transcribed but not translated (Table 1)

Summary

Chromatin Remodeling in the Noncoding Repeat Expansion Diseases*

Daman Kumari and Karen Usdin From the Section on Gene Structure and Disease, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830. Friedreich ataxia, myotonic dystrophy type 1 and 3 forms of intellectual disability, fragile X syndrome, FRAXE mental retardation, and FRA12A mental retardation are repeat expansion diseases caused by expansion of CTG1⁄7CAG, GAA1⁄7TTC, or CGG1⁄7CCG repeat tracts. These repeats are transcribed but not translated. They are located in different parts of different genes and cause symptoms that range from ataxia and hypertrophic cardiomyopathy to muscle wasting, male infertility, and mental retardation, yet recent reports suggest that, despite these differences, the repeats may share a common property, namely the ability to initiate repeat-mediated epigenetic changes that result in heterochromatin formation

Background

FRAXE MR

Mutation type LOFa LOF LOF LOF

These Repeats Do Share a Common Property