1. Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.
- Author
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Helmlinger D, Hardy S, Sasorith S, Klein F, Robert F, Weber C, Miguet L, Potier N, Van-Dorsselaer A, Wurtz JM, Mandel JL, Tora L, and Devys D
- Subjects
- Amino Acid Sequence, Ataxin-7, Cell Cycle Proteins, Cell Line, Conserved Sequence, Histone Acetyltransferases, Humans, Molecular Sequence Data, Multiprotein Complexes chemistry, Multiprotein Complexes metabolism, Mutation, Nerve Tissue Proteins chemistry, Nerve Tissue Proteins genetics, Protein Binding, Protein Structure, Tertiary, Protein Subunits chemistry, Protein Subunits genetics, Sequence Homology, Amino Acid, TATA-Binding Protein Associated Factors metabolism, Transcription Factor TFIID metabolism, Transcription Factors, Transcription, Genetic, Zinc metabolism, p300-CBP Transcription Factors, Acetyltransferases metabolism, Nerve Tissue Proteins metabolism, Protein Subunits metabolism, Trans-Activators metabolism
- Abstract
Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene leading to elongation of a polyglutamine tract in ataxin-7, a protein of unknown function. A putative ataxin-7 yeast orthologue (SGF73) has been identified recently as a new component of the SAGA (Spt/Ada/Gcn5 acetylase) multisubunit complex, a coactivator required for transcription of a subset of RNA polymerase II-dependent genes. We show here that ataxin-7 is an integral component of the mammalian SAGA-like complexes, the TATA-binding protein-free TAF-containing complex (TFTC) and the SPT3/TAF9/GCN5 acetyltransferase complex (STAGA). In agreement, immunoprecipitation of ataxin-7 retained a histone acetyltransferase activity, characteristic for TFTC-like complexes. We further identified a minimal domain in ataxin-7 that is required for interaction with TFTC/STAGA subunits and is conserved highly through evolution, allowing the identification of a SCA7 gene family. We showed that this domain contains a conserved Cys(3)His motif that binds zinc, forming a new zinc-binding domain. Finally, polyglutamine expansion in ataxin-7 did not affect its incorporation into TFTC/STAGA complexes purified from SCA7 patient cells. We demonstrate here that ataxin-7 is the human orthologue of the yeast SAGA SGF73 subunit and is a bona fide subunit of the human TFTC-like transcriptional complexes.
- Published
- 2004
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