title: Ancient repeated DNA elements and the regulation of the human frataxin promoter.
abstract: Friedreich ataxia results from frataxin insufficiency caused by repeat expansion in intron 1 of the frataxin gene. Since the coding sequence is unchanged, the potential exists to ameliorate symptoms by increasing frataxin promoter activity. We therefore defined the minimal frataxin promoter in humans. Despite the fact that frataxin is an essential gene, its promoter is not well conserved in mammals, in part because it has been the frequent target of retroelement insertions. Most of the activity of the human frataxin promoter can be attributed to these retroelements, illustrating how these elements, considered parasitic by some, have been co-opted to drive critical genes. Individuals with the milder French Acadian form and those with the classic form of the disease have no biologically relevant sequence differences in the promoter or 3' UTR, suggesting that some other region of the gene, perhaps the repeat itself, is responsible for the difference in disease severity.
authors.affiliation: Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
authors.forename: Eriko
authors.initials: E
authors.lastname: Greene
authors.forename: Ali
authors.initials: A
authors.lastname: Entezam
authors.forename: Daman
authors.initials: D
authors.lastname: Kumari
authors.forename: Karen
authors.initials: K
authors.lastname: Usdin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence; D005621:Friedreich Ataxia / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000096923:Frataxin
chemical_list: D020413:3' Untranslated Regions; D033862:Iron-Binding Proteins; D014157:Transcription Factors; D000096923:Frataxin