title: Transcriptional alterations and chromatin remodeling in polyglutamine diseases.
abstract: Transcriptional dysregulation is now thought to be a common feature of polyglutamine disorders, including the spinocerebellar ataxias (SCAs). However, the precise causes of transcriptional alterations and how they relate to the observed phenotype remain elusive. Transcriptional impairment differs in different diseases, possibly reflecting the specific functions of the disease-causing proteins. The SCA7 gene product, ataxin-7, is a subunit of a transcriptional coactivator complex (called STAGA or TFTC) that has histone acetyltransferase activity. Studies on the effect of mutant ataxin-7 on STAGA function suggest that chromatin remodeling and transcriptional alterations are key pathologic events in SCA type 7. These studies could reveal how polyglutamine expansions alter the transcriptional regulation of genes required for neuronal function.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Helmlinger
authors.forename: Làszlò
authors.initials: L
authors.lastname: Tora
authors.forename: Didier
authors.initials: D
authors.lastname: Devys
mesh_terms: D000818:Animals; D000067719:Ataxin-7; D042002:Chromatin Assembly and Disassembly; D042622:DNA Repeat Expansion; D006801:Humans; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; C000593831:Atxn7 protein, mouse; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine