ArticleNucleic acids research2011
Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- BRD4 recruitment into HP1 condensates desilences transcription without erasure of repressive chromatin.Nature cell biology · 2026Article
- Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich's ataxia.Molecular cell · 2026Article
- Modeling Friedreich's ataxia with Bergmann glia-enriched human cerebellar organoids.Communications biology · 2026Article
- Simple sequence repeats and their expansions: role in plant development, environmental response and adaptation.The New phytologist · 2025Review
- Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases.Biomolecules · 2024Review
- The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Structure and Dynamics of DNA and RNA Double Helices Formed by d(CTG), d(GTC), r(CUG), and r(GUC) Trinucleotide Repeats and Associated DNA-RNA Hybrids.The journal of physical chemistry. B · 2023Article
- Premature transcription termination at the expanded GAA repeats and aberrant alternative polyadenylation contributes to the Frataxin transcriptional deficit in Friedreich's ataxia.Human molecular genetics · 2022Article
- DNA methylation in Friedreich ataxia silences expression of frataxin isoform E.Scientific reports · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
- Molecular mechanisms underlying nucleotide repeat expansion disorders.Nature reviews. Molecular cell biology · 2021Review
- Reverse Phase Protein Array Reveals Correlation of Retinoic Acid Metabolism With Cardiomyopathy in Friedreich's Ataxia.Molecular & cellular proteomics : MCP · 2021Article
- Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich's ataxia patient cells.The Journal of biological chemistry · 2020Article
- Oxidative Stress in DNA Repeat Expansion Disorders: A Focus on NRF2 Signaling Involvement.Biomolecules · 2020Review
- Molecular Mechanisms and Therapeutics for the GAA·TTC Expansion Disease Friedreich Ataxia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- The impact of histone post-translational modifications in neurodegenerative diseases.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Targeted Oligonucleotides for Treating Neurodegenerative Tandem Repeat Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- FAST-1 antisense RNA epigenetically alters FXN expression.Scientific reports · 2018Article
- Structure and Dynamics of DNA and RNA Double Helices Obtained from the CCG and GGC Trinucleotide Repeats.The journal of physical chemistry. B · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Friedreich's ataxia (FRDA) is caused by biallelic expansion of GAA repeats leading to the transcriptional silencing of the frataxin (FXN) gene. The exact molecular mechanism of inhibition of FXN expression is unclear. Herein, we analyze the effects of hyperexpanded GAA repeats on transcription status and chromatin modifications proximal and distal to the GAA repeats. Using chromatin immunoprecipitation and quantitative PCR we detected significant changes in the chromatin landscape in FRDA cells relative to control cells downstream of the promoter, especially in the vicinity of the GAA tract. In this region, hyperexpanded GAAs induced a particular constellation of histone modifications typically associated with heterochromatin-like structures. Similar epigenetic changes were observed in GFP reporter construct containing 560 GAA repeats. Furthermore, we observed similar levels of FXN pre-mRNA at a region upstream of hyperexpanded GAA repeats in FRDA and control cells, indicating similar efficiency of transcription initiation. We also demonstrated that histone modifications associated with hyperexpanded GAA repeats are independent of initiation and progression of transcription. Our data provide strong evidence that FXN deficiency in FRDA patients results from a block of transition from initiation to a productive elongation of FXN transcription due to heterochromatin-like structures formed in the proximity of the hyperexpanded GAAs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.