Altered nucleosome positioning at the transcription start site and deficient transcriptional initiation in friedreich ataxia

Abstract

Background: Friedreich ataxia (FRDA) is caused by an expanded GAA triplet repeat (GAA-TR) mutation that results in FXN transcriptional deficiency. Results: Repressive chromatin spreads from the expanded GAA-TR mutation, switching off the FXN gene promoter. Conclusion: Reduced transcriptional initiation is the major cause of FXN transcriptional deficiency in FRDA. Significance: Reactivation of FXN transcriptional initiation is a potential therapeutic strategy in FRDA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.