ArticlePloS one2010
Expression of human frataxin is regulated by transcription factors SRF and TFAP2.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Frataxin mRNA isoforms in FRDA patients and normal subjects: effect of tocotrienol supplementation.BioMed research international · 2013Trial
- The Regulation of the Disease-Causing GeneCells · 2024Review
- SIRT3 Regulates Clearance of Apoptotic Cardiomyocytes by Deacetylating Frataxin.Circulation research · 2023Article
- Removal of the GAA repeat in the heart of a Friedreich's ataxia mouse model using CjCas9.Gene therapy · 2023Article
- FDX2 and ISCU Gene Variations Lead to Rhabdomyolysis With Distinct Severity and Iron Regulation.Neurology. Genetics · 2022Article
- Genome-Wide Analysis and the Expression Pattern of the MADS-Box Gene Family inPlants (Basel, Switzerland) · 2021Article
- Review
- Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase.Molecular and cellular biology · 2020Article
- Frataxin gene editing rescues Friedreich's ataxia pathology in dorsal root ganglia organoid-derived sensory neurons.Nature communications · 2020Article
- Defining Transcription Regulatory Elements in the Human Frataxin Gene: Implications for Gene Therapy.Human gene therapy · 2020Article
- Analysis of Putative Epigenetic Regulatory Elements in theInternational journal of molecular sciences · 2020Review
- FAST-1 antisense RNA epigenetically alters FXN expression.Scientific reports · 2018Article
- Increased Frataxin Expression Induced in Friedreich Ataxia Cells by Platinum TALE-VP64s or Platinum TALE-SunTag.Molecular therapy. Nucleic acids · 2018Article
- Cytokine therapy-mediated neuroprotection in a Friedreich's ataxia mouse model.Annals of neurology · 2017Article
- Excision of Expanded GAA Repeats Alleviates the Molecular Phenotype of Friedreich's Ataxia.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Epigenetic-based therapies for Friedreich ataxia.Frontiers in genetics · 2014Review
- Inhibition of the function of class IIa HDACs by blocking their interaction with MEF2.Nucleic acids research · 2012Article
- Is Friedreich ataxia an epigenetic disorder?Clinical epigenetics · 2012Article
- Long range regulation of human FXN gene expression.PloS one · 2011Article
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundFriedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression. METHODOLOGY/PRINCIPAL
findingsWe utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2. CONCLUSIONS/SIGNIFICANCE: We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia.
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Registered trials
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.