The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6).
Mutations in THAP1 have been associated with dystonia 6. THAP1 encodes a transcription factor with mostly unknown targets. We tested the hypothesis that THAP1 regulates the expression of DYT1 (TOR1A), another dystonia-causing gene. After characterization of the TOR1A promoter, we demonstrate that THAP1 binds to the core promoter of TOR1A. Further, we report that wild type THAP1 represses the expression of TOR1A, whereas dystonia 6-associated mutant THAP1 results in decreased repression of TOR1A. Our data demonstrate that THAP1 regulates the transcription of TOR1A, suggesting transcriptional dysregulation as a cause of dystonia.
Institute of Human Genetics, University of Lübeck, Lübeck, Germany.
Frank J
FJ
Kaiser
Alma
A
Osmanoric
Aleksandar
A
Rakovic
Alev
A
Erogullari
Nils
N
Uflacker
Diana
D
Braunholz
Thora
T
Lohnau
Slobodanka
S
Orolicki
Melanie
M
Albrecht
Gabriele
G
Gillessen-Kaesbach
Christine
C
Klein
Katja
K
Lohmann
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020821:Dystonic Disorders / Q000235:genetics* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C474080:THAP1 protein, human; C108175:TOR1A protein, human