title: Direct interaction between causative genes of DYT1 and DYT6 primary dystonia.
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.
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gavarini
authors.forename: Corinne
authors.initials: C
authors.lastname: Cayrol
authors.forename: Tania
authors.initials: T
authors.lastname: Fuchs
authors.forename: Natalia
authors.initials: N
authors.lastname: Lyons
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Ehrlich
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Girard
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / 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; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D014471:Umbilical Veins
chemical_list: 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