Abstract
Primary dystonia is a movement disorder characterized by sustained muscle contractions and in which dystonia is the only or predominant clinical feature. TOR1A(DYT1) and the transcription factor THAP1(DYT6) are the only genes identified thus far for primary dystonia. Using electromobility shift assays and chromatin immunoprecipitation (ChIP) quantitative polymerase chain reaction (qPCR), we demonstrate a physical interaction between THAP1 and the TOR1A promoter that is abolished by pathophysiologic mutations. Our findings provide the first evidence that causative genes for primary dystonia intersect in a common pathway and raise the possibility of developing novel therapies targeting this pathway.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Animals
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Apoptosis Regulatory Proteins / genetics*
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Apoptosis Regulatory Proteins / metabolism*
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Brain / metabolism
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Cell Nucleus / metabolism
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Cells, Cultured
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Chromatin Immunoprecipitation / methods
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Dystonic Disorders / genetics*
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Dystonic Disorders / pathology
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Electrophoretic Mobility Shift Assay / methods
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Endothelial Cells / drug effects
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Endothelial Cells / ultrastructure
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Female
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Fibroblasts / metabolism
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Fibroblasts / ultrastructure
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics*
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Glioblastoma / pathology
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Humans
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Male
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Mice
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Middle Aged
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Molecular Chaperones / genetics*
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Molecular Chaperones / metabolism*
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Mutation / genetics
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Promoter Regions, Genetic / physiology
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Protein Binding
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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RNA, Small Interfering / pharmacology
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Transfection / methods
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Umbilical Veins
Substances
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Apoptosis Regulatory Proteins
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DNA-Binding Proteins
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Molecular Chaperones
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Nuclear Proteins
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RNA, Messenger
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RNA, Small Interfering
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THAP1 protein, human
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TOR1A protein, human