title: The human MJD gene: genomic structure and functional characterization of the promoter region.
abstract: Machado-Joseph disease (MJD) is a progressive neurodegenerative disorder caused by expansion of a CAG motif within the translated region of the human MJD (hMJD) gene which has been mapped to chromosome 14q. In this study, the hMJD gene was identified in two overlapping bacterial artificial chromosome (BAC) clones and contained 11 exons resulting in a 6.14 kb transcript. The 5'-flanking region of the hMJD gene included a TATA-less promoter with GC-rich regions, a CCAAT box and multiple potential SP1 binding sites. Luciferase reporter assays performed in neuronal and non-neuronal human cell lines demonstrated a core promoter within the 200 bp region immediately upstream of the putative transcriptional start site (-89 according to the start codon). DNA-protein interactions defined by electrophoretic mobility shift assays (EMSA) revealed specific binding of nuclear proteins to the putative core promoter region.
authors.affiliation: Department of Neurology, Neurobiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. i.schmitt@uni-bonn.de
authors.forename: Ina
authors.initials: I
authors.lastname: Schmitt
authors.forename: Bernd O
authors.initials: BO
authors.lastname: Evert
authors.forename: Hassan
authors.initials: H
authors.lastname: Khazneh
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wuellner
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000067699:Ataxin-3; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005796:Genes / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D004247:DNA; D008156:Luciferases; C092341:ATXN3 protein, human; D000067699:Ataxin-3