The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)

Frank J. Kaiser; Alma Osmanoric; Aleksandar Rakovic; Alev Erogullari; Nils Uflacker; Diana Braunholz; Thora Lohnau; Slobodanka Orolicki; Melanie Albrecht; Gabriele Gillessen-Kaesbach; Christine Klein; Katja Lohmann

doi:10.1002/ana.22157

The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)

Frank J. Kaiser, Alma Osmanoric, Aleksandar Rakovic, Alev Erogullari, Nils Uflacker, Diana Braunholz, Thora Lohnau, Slobodanka Orolicki, Melanie Albrecht, Gabriele Gillessen-Kaesbach, Christine Klein^*, Katja Lohmann

^*Corresponding author for this work

62 Citations (Scopus)

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.

Original language	English
Journal	Annals of Neurology
Volume	68
Issue number	4
Pages (from-to)	554-559
Number of pages	6
ISSN	0364-5134
DOIs	https://doi.org/10.1002/ana.22157
Publication status	Published - 01.10.2010

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title = "The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)",

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.",

author = "Kaiser, {Frank J.} and Alma Osmanoric and Aleksandar Rakovic and Alev Erogullari and Nils Uflacker and Diana Braunholz and Thora Lohnau and Slobodanka Orolicki and Melanie Albrecht and Gabriele Gillessen-Kaesbach and Christine Klein and Katja Lohmann",

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T1 - The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)

AU - Kaiser, Frank J.

AU - Osmanoric, Alma

AU - Rakovic, Aleksandar

AU - Erogullari, Alev

AU - Uflacker, Nils

AU - Braunholz, Diana

AU - Lohnau, Thora

AU - Orolicki, Slobodanka

AU - Albrecht, Melanie

AU - Gillessen-Kaesbach, Gabriele

AU - Klein, Christine

AU - Lohmann, Katja

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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.

AB - 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.

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SN - 0364-5134

VL - 68

SP - 554

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JO - Annals of Neurology

JF - Annals of Neurology

IS - 4

ER -

The dystonia gene DYT1 is repressed by the transcription factor THAP1 (DYT6)

Abstract

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