title: Ataxin-1 occupies the promoter region of E-cadherin in vivo and activates CtBP2-repressed promoter.
abstract: Ataxin-1 is a polyglutamine protein of unknown function that is encoded by the ATXN1 gene in humans. To gain insight into the function of ataxin-1, we sought to identify proteins that interact with ataxin-1 through yeast two-hybrid screening. In this study, transcriptional corepressor CtBP2 was identified as a protein that interacted with ataxin-1. CtBP2 and ataxin-1 colocalized in the nucleus of mammalian cells. Since the E-cadherin promoter is a target of CtBP-mediated repression, the relationship between ataxin-1 and the E-cadherin promoter was investigated. Chromatin immunoprecipitation assays showed that CtBP2 and ataxin-1 were recruited to the E-cadherin promoter in mammalian cells. Luciferase assays using E-cadherin promoter reporter constructs revealed that the luciferase activity was enhanced as the level of ataxin-1 protein expression increased. CtBP2 overexpression decreased E-cadherin expression, but expression of ataxin-1 inversely increased the mRNA and protein levels of endogenous E-cadherin. Interestingly, siRNA experiments showed that the transcriptional activation of ataxin-1 was associated with the presence of CtBP2. This study demonstrates that ataxin-1 occupies the promoter region of E-cadherin in vivo and that ataxin-1 activates the promoter in a CtBP2-mediated transcriptional regulation manner. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 1, 5ka, Anam-dong, Sungbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lee
authors.forename: Sunghoi
authors.initials: S
authors.lastname: Hong
authors.forename: Sungsu
authors.initials: S
authors.lastname: Kim
authors.forename: Seongman
authors.initials: S
authors.lastname: Kang
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD; D000067696:Ataxin-1; D000067528:Ataxins; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins; D006801:Humans; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C000593749:ATXN1 protein, human; D015703:Antigens, CD; D000067696:Ataxin-1; D000067528:Ataxins; C513384:CDH1 protein, human; D015820:Cadherins; D056970:Co-Repressor Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human