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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Polyglutamine tracts as modulators of transcriptional activation from yeast to mammals

Lilit Atanesyan1, 2 / Viola Günther1 / Bernhard Dichtl1 / Oleg Georgiev1 / 1

1Institute of Molecular Life Sciences, University of Zürich, CH-8057 Zürich, Switzerland

2Life Science Zurich Graduate School, University of Zürich/ETH Zürich, CH-8057 Zürich, Switzerland

Corresponding author

Citation Information: . Volume 393, Issue 1-2, Pages 63–70, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC-2011-252, January 2012

Publication History

Received:
2011-11-08
Accepted:
2011-11-09

Abstract

Microsatellite 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.

Keywords: Drosophila; evolvability; polyglutamine repeat; Saccharomyces cerevisiae; transcription factor; triplet repeat

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