Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes.
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.[1]References
- Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes. Helmlinger, D., Hardy, S., Eberlin, A., Devys, D., Tora, L. Biochem. Soc. Symp. (2006) [Pubmed]
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