title: Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation.
abstract: Transcriptional dysregulation, particularly cAMP-responsive-element-mediated transcriptional repression, has been implicated in expanded polyglutamine diseases. However, it has not been clarified whether this transcriptional repression is a cause or result of neurodegeneration. Furthermore, the association between aggregates of expanded polyglutamine stretches and transcriptional repression is not clear. We established isogenic cell lines with polyglutamine stretches, which also expressed d2EGFP under the control of cAMP-responsive elements. In this system, the polyglutamine stretch repressed cAMP-responsive-element-mediated transcription without the formation of macroscopic expanded polyglutamine aggregates. Furthermore, aggregate formation did not have an adverse effect on the repression of transcriptional activity. The results demonstrated that the repression of cAMP-responsive-element-mediated transcription is an early event caused by a soluble form of polyglutamine stretch.
authors.affiliation: Department of Neurology, Resource Branch for Brain Disease Research, Center for Bioresource-Based Research, Brain Research Institute, Niigata University, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Nozaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
mesh_terms: D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003952:Diagnostic Imaging; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004347:Drug Interactions; D019793:Fluorescein / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection / Q000379:methods
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010455:Peptides; C097188:polyglutamine; D000242:Cyclic AMP; D004318:Doxycycline; D019793:Fluorescein