Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity

摘要: Histone acetyltransferases have been shown to participate in many essential cellular processes, particularly those associated with activation of transcription. SAGA (Spt-Ada-Gcn5 acetyltransferase) and SLIK (SAGA-like) are two highly homologous multisubunit histone acetyltransferase complexes that were originally identified the yeast Saccharomyces cerevisiae. Here, we identify protein Sgf73/Sca7 as a component SLIK, homologue human SCA7-encoded ataxin-7, which, its polyglutamine expanded pathological form, is responsible for neurodegenerative disease spinocerebellar ataxia 7 (SCA7). Our findings indicate Sca7 necessary integrity function both ataxin-7 able compliment loss yeast. A polyglutamine-expanded version assembles complex depleted critical proteins regulate ability acetylate nucleosomes. These observations significant implications pathogenesis.