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Polyglutamine tracts as modulators of transcriptional activation from yeast to mammals
journal contribution
posted on 2012-01-01, 00:00 authored by L Atanesyan, V Günther, Bernhard DichtlBernhard Dichtl, O Georgiev, W SchaffnerMicrosatellite repeats are genetically unstable and subject to expansion and shrinkage. A subset of them, triplet repeats, can occur within the coding region and specify homomeric tracts of amino acids. Polyglutamine (polyQ) tracts are enriched in eukaryotic regulatory proteins, notably transcription factors, and we had shown before that they can contribute to transcriptional activation in mammalian cells. Here we generalize this finding by also including evolutionarily divergent organisms, namely, Drosophila and baker's yeast. In all three systems, Gal4-based model transcription factors were more active if they harbored a polyQ tract, and the activity depended on the length of the tract. By contrast, a polyserine tract was inactive. PolyQs acted from either an internal or a C-terminal position, thus ruling out a merely structural 'linker' effect. Finally, a two-hybrid assay in mammalian cells showed that polyQ tracts can interact with each other, supporting the concept that a polyQ-containing transcription factor can recruit other factors with polyQ tracts or glutamine-rich activation domains. The widespread occurrence of polyQ repeats in regulatory proteins suggests a beneficial role; in addition to the contribution to transcriptional activity, their genetic instability might help a species to adapt to changing environmental conditions in a potentially reversible manner.
History
Journal
Biological chemistryVolume
393Issue
1-2Pagination
63 - 70Publisher
Walter de Gruyter GmbH & Co. KGLocation
Berlin, GermanyPublisher DOI
ISSN
1431-6730eISSN
1437-4315Language
engPublication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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No categories selectedKeywords
Drosophilaevolvabilitytriplet repeattranscription factorSaccharomyces cerevisiaepolyglutamine repeatScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyINCLUSION-BODY FORMATIONHUNTINGTONS-DISEASENEURODEGENERATIVE DISEASESEXPANDED POLYGLUTAMINETRINUCLEOTIDE REPEATSNEURONAL DEATHHUMAN GENOMEDNA REPEATSGLUTAMINELENGTH
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