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Expanded GAA repeats impair FXN gene expression and reposition the FXN locus to the nuclear lamina in single cells

Abnormally expanded DNA repeats are associated with several neurodegenerative diseases. In Friedreich's ataxia (FRDA), expanded GAA repeats in intron 1 of the frataxin gene (FXN) reduce FXN mRNA levels in averaged cell samples through a poorly understood mechanism. By visualizing FXN expression and nuclear localization in single cells, we show that GAA-expanded repeats decrease the number of FXN mRNA molecules, slow transcription, and increase FXN localization at the nuclear lamina (NL). Restoring histone acetylation reverses NL positioning. Expanded GAA-FXN loci in FRDA patient cells show increased NL localization with increased silencing of alleles and reduced transcription from alleles positioned peripherally. 

Read More: Expanded GAA repeats impair FXN gene expression and reposition the FXN locus to the nuclear lamina in single cells


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Jen Farmer

Jen Farmer

Executive Director

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