Repeat expansion affects both transcription initiation and elongation in friedreich ataxia cells.

ABSTRACT: Expansion of a GAA · TTC repeat in the first intron of the frataxin (FXN) gene causes an mRNA deficit that results in Friedreich ataxia (FRDA). The region flanking the repeat on FRDA alleles is associated with more extensive DNA methylation than is seen on normal alleles and histone modifications typical of repressed genes. However, whether these changes are responsible for the mRNA deficit is controversial. Using chromatin immunoprecipitation and cell lines from affected and unaffected individuals, we show that certain marks of active chromatin are also reduced in the promoter region of the FXN gene in patient cells. Thus, the promoter chromatin may be less permissive for transcription initiation than it is on normal alleles. Furthermore, we show that the initiating form of RNA polymerase

SUBMITTER: Kumari D 

PROVIDER: S-EPMC3039332 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature