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

Dominique Helmlinger; Sara Hardy; Adrien Eberlin; Didier Devys; Làszlò Tora

doi:10.1042/bss0730155

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

Biochem Soc Symp. 2006:(73):155-63. doi: 10.1042/bss0730155.

Authors

Dominique Helmlinger¹, Sara Hardy, Adrien Eberlin, Didier Devys, Làszlò Tora

Affiliation

¹ Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, CNRS/IN SER M/ULP, BP 10142, 67404 Illkirch Cedex, France.

PMID: 16626296
DOI: 10.1042/bss0730155

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ataxin-7
Cell Cycle Proteins / chemistry*
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
HeLa Cells
Histone Acetyltransferases / chemistry*
Histone Acetyltransferases / genetics
Histone Acetyltransferases / metabolism*
Humans
Multiprotein Complexes
Nerve Tissue Proteins / chemistry*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Peptides / chemistry
Peptides / genetics
Protein Subunits
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Spinocerebellar Ataxias / etiology
Spinocerebellar Ataxias / genetics
Spinocerebellar Ataxias / metabolism
Trans-Activators / chemistry
Trans-Activators / genetics
Trans-Activators / metabolism
Transcription Factors / chemistry*
Transcription Factors / genetics
Transcription Factors / metabolism*
p300-CBP Transcription Factors

Substances

ATXN7 protein, human
Ataxin-7
Cell Cycle Proteins
Multiprotein Complexes
Nerve Tissue Proteins
Peptides
Protein Subunits
SAGA complex, S cerevisiae
Saccharomyces cerevisiae Proteins
Trans-Activators
Transcription Factors
polyglutamine
Histone Acetyltransferases
p300-CBP Transcription Factors
p300-CBP-associated factor