Ataxin-3 Is a Histone-binding Protein with Two Independent Transcriptional Corepressor Activities

摘要: The mechanisms of pathology for the family polyglutamine disease proteins are unknown; however, recently it was shown that several these inhibit transcription suggesting transcriptional repression may be a potential mechanism pathology. In present study we use cell transfections, in vitro binding, co-immunoprecipitations, and reporter assays to show protein, ataxin-3, interacts with major histone acetyltransferases cAMP-response-element binding protein (CREB)-binding p300, p300/CREB-binding protein-associated factor inhibits by coactivators. Importantly, endogenous ataxin-3 is co-immunoprecipitated each coactivators non-transfected cells. C-terminal polyglutamine-containing domain coactivator-dependent required N-terminal acetylation p300 vivo. Histone blocking access sites on histones appears inhibition. Together, our data provide novel regulation involves targeting histones, coactivators, an independent mode direct transcription, suggests its physiological function possibly pathological effects linked interactions proteins.