Fiche publication
Date publication
juin 2004
Journal
Human molecular genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DEVYS Didier
,
Pr MANDEL Jean-Louis
,
Dr TORA Laszlo
,
Dr VAN DORSSELAER Alain
,
Dr MIGUET Laurent
Tous les auteurs :
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, Devys D
Lien Pubmed
Résumé
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.
Mots clés
Acetyltransferases, metabolism, Amino Acid Sequence, Ataxin-7, Cell Cycle Proteins, Cell Line, Conserved Sequence, Histone Acetyltransferases, Humans, Molecular Sequence Data, Multiprotein Complexes, chemistry, Mutation, Nerve Tissue Proteins, chemistry, Protein Binding, Protein Structure, Tertiary, Protein Subunits, chemistry, Sequence Homology, Amino Acid, TATA-Binding Protein Associated Factors, metabolism, Trans-Activators, metabolism, Transcription Factor TFIID, metabolism, Transcription Factors, Transcription, Genetic, Zinc, metabolism, p300-CBP Transcription Factors
Référence
Hum. Mol. Genet.. 2004 Jun;13(12):1257-65
