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The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)
Author(s) -
Kaiser Frank J.,
Osmanoric Alma,
Rakovic Aleksandar,
Erogullari Alev,
Uflacker Nils,
Braunholz Diana,
Lohnau Thora,
Orolicki Slobodanka,
Albrecht Melanie,
GillessenKaesbach Gabriele,
Klein Christine,
Lohmann Katja
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22157
Subject(s) - transcription factor , psychological repression , dystonia , gene , mutant , transcription (linguistics) , biology , genetics , mutation , gene expression , neuroscience , linguistics , philosophy
Abstract 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. Ann Neurol 2010;68:554–559