HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model.

ABSTRACT:

Background

Friedreich ataxia, an autosomal recessive neurodegenerative and cardiac disease, is caused by abnormally low levels of frataxin, an essential mitochondrial protein. All Friedreich ataxia patients carry a GAATTC repeat expansion in the first intron of the frataxin gene, either in the homozygous state or in compound heterozygosity with other loss-of-function mutations. The GAA expansion inhibits frataxin expression through a heterochromatin-mediated repression mechanism. Histone modifications that are characteristic of silenced genes in heterochromatic regions occur at expanded alleles in cells from Friedreich ataxia patients, including increased trimethylation of histone H3 at lysine 9 and hypoacetylation of histones H3 and H4.

Methodology/principal findings

By chr

SUBMITTER: Rai M 

PROVIDER: S-EPMC2373517 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature