Both normal and polyglutamine-expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase-containing complexes

摘要

SCA7 (spinocerebellar ataxia type 7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene that leads to elongation of a polyglutamine tract in ataxin-7,a protein of unknown function.Sgf73,a putative yeast orthologue of ataxin-7,has been identified as a new component of the yeast SAGA (Spt/Ada/Gcn5 acetyltransferase) multisubunit complex,a co-activator required for the transcription of a subset of RNA polymerase II-dependent genes.We show here that ataxin-7 is an integral component of mammalian SAGA-like complexes,i.e.the TFTC [TBP (TATA-binding protein)-free TAF (TBP-associated factor) complex] and the STAGA (SPT3/TAF9/GCN5 acetyltransferase) complex.In agreement with this,immunoprecipitation of ataxin-7 retained a histone acetyltransferase activity characteristic of TFTC-like complexes.Moreover,polyglutamine expansion in ataxin-7 did not affect its incorporation into TFTCs/STAGA complexes purified from cells from a SCA7 patient.We demonstrate here that ataxin-7 is the human orthologue of a the yeast SAGA Sgf73 subunit,and is a bona fide subunit of human TFTC-like transcriptional complexes.