A role for both wild-type and expanded ataxin-7 in transcriptional regulation
2005 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 20, no 3, 646-655 p.Article in journal (Refereed) Published
Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease primarily affecting the brainstem, retina and Purkinje cells of the cerebellum. The disease is caused by a polyglutamine expansion in ataxin-7, a protein found in two complexes TFTC and STAGA, involved in transcriptional regulation. Transcriptional dysregulation has been implicated in the pathology of several polyglutamine diseases. In this paper, we analyzed the effect of both wild-type and expanded ataxin-7 on transcription driven by the co-activator CBP and the Purkinje cell expressed nuclear receptor RORα1. We could show that transcription mediated by both CBP and RORα1 was repressed by expanded ataxin-7. Interestingly, repression of transcription could also be observed with wild-type full-length ataxin-7, not only on CBP- and RORα1-mediated transcription, but also on basal transcription. The repression could be counteracted by inhibition of deacetylation, suggesting that ataxin-7 may act as a repressor of transcription by inhibiting the acetylation activity of TFTC and STAGA.
Place, publisher, year, edition, pages
2005. Vol. 20, no 3, 646-655 p.
spinocerebellar ataxia type 7, polyglutamine, CAG repeat, acetylation, CREB-binding protein/genetics, cell nucleus/genetics/metabolism, cerebellum/*metabolism/pathology/physiopathology, child, histones/metabolism, humans, male, mutation/genetics, nerve tissue proteins/*genetics, promoter regions (genetics)/genetics, purkinje cells/metabolism/pathology, receptor protein-tyrosine kinases, receptors; cell surface/genetics, regulatory elements; transcriptional/*genetics, repressor proteins/genetics, silencer elements, transcriptional/genetics, spinocerebellar ataxias/*genetics/metabolism/physiopathology, trans-activation (genetics)/genetics, trinucleotide repeat expansion/genetics, tumor cells, cultured
IdentifiersURN: urn:nbn:se:umu:diva-3802DOI: 10.1016/j.nbd.2005.04.018PubMedID: 15936949OAI: oai:DiVA.org:umu-3802DiVA: diva2:142677