Ataxin-7 (ATXN7) is a nuclear protein and integral component of the SAGA (Spt-Ada-Gcn5 acetyltransferase) chromatin remodeling complex, which regulates transcription through histone acetylation and deubiquitination. CAG repeat expansion in ATXN7 causes Spinocerebellar Ataxia Type 7 (SCA7), a distinctive ataxia characterized by progressive cerebellar degeneration and retinal cone-rod dystrophy.[1]
Ataxin-7 contains:
The protein's integration into the SAGA complex is essential for its normal function and contributes to disease pathogenesis when mutated.[2]
Ataxin-7 is a core subunit of the SAGA transcriptional coactivator:
SAGA with ataxin-7 regulates:[3]
Ataxin-7 is particularly important in photoreceptors:
CAG expansion in ATXN7 causes:
SCA7 is unique among SCAs for its retinal involvement:
Brain regions affected:
Given SAGA dysfunction in SCA7:[5]
| Strategy | Mechanism | Status |
|---|---|---|
| ASOs | Reduce ATXN7 expression | Preclinical |
| RNAi | Allele-selective knockdown | Preclinical |
| CRISPRi | Transcriptional repression | Discovery |
| Partner | Function | Disease Relevance |
|---|---|---|
| GCN5 | Histone acetyltransferase | Transcriptional dysregulation |
| USP22 | Deubiquitinase | SAGA complex function |
| TAF10 | TFIID component | Transcription initiation |
| CBP/p300 | Histone acetyltransferase | Sequestration in inclusions |
David G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nature Genetics. 1997. ↩︎
Helmlinger D, et al. Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes. Human Molecular Genetics. 2004. ↩︎
McMahon SJ, et al. The novel basal transcription factor TFIIS-related protein is required for craniofacial development. Development. 2011. ↩︎
Ström AL, et al. Transcriptional alterations in the cerebellum of SCA7 patients and the SCA7 mouse model. Acta Neuropathologica. 2012. ↩︎
Mookherjee P, et al. HDAC inhibitor restores normal histone acetylation in SCA7 and improves cerebellar pathology. Annals of Neurology. 2011. ↩︎