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- Title
Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.
- Authors
Helmlinger, Dominique; Hardy, Sara; Sasorith, Souphatta; Klein, Fabrice; Robert, Flavie; Weber, Chantal; Miguet, Laurent; Potier, Noëlle; Van-Dorsselaer, Alain; Wurtz, Jean-Marie; Mandel, Jean-Louis; Tora, Làszlò; Devys, Didier
- 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.
- Publication
Human molecular genetics, 2004, Vol 13, Issue 12, p1257
- ISSN
0964-6906
- Publication type
Journal Article
- DOI
10.1093/hmg/ddh139