title: A role for both wild-type and expanded ataxin-7 in transcriptional regulation.
abstract: 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 RORalpha1. We could show that transcription mediated by both CBP and RORalpha1 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 RORalpha1-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.
authors.affiliation: Department of Medical Biosciences, Unit of Medical and Clinical Genetics, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Ström
authors.forename: Lars
authors.initials: L
authors.lastname: Forsgren
authors.forename: Monica
authors.initials: M
authors.lastname: Holmberg
mesh_terms: D000107:Acetylation; D000067719:Ataxin-7; D050882:CREB-Binding Protein / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D037941:Silencer Elements, Transcriptional / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015533:Transcriptional Activation / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D006657:Histones; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C078716:ROR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors