Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.
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.
Helmlinger
Dominique
D
Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
Hardy
Sara
S
Sasorith
Souphatta
S
Klein
Fabrice
F
Robert
Flavie
F
Weber
Chantal
C
Miguet
Laurent
L
Potier
Noëlle
N
Van-Dorsselaer
Alain
A
Wurtz
Jean-Marie
JM
Mandel
Jean-Louis
JL
Tora
Làszlò
L
Devys
Didier
D
D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000067719:Ataxin-7; D018797:Cell Cycle Proteins; D002460:Cell Line; D017124:Conserved Sequence; D051548:Histone Acetyltransferases; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D000067719:Ataxin-7; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D015032:Zinc; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000593829:ATXN7 protein, human; C089768:TAF10 protein, human; C501179:KAT2A protein, human