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| Subject Categories: Chromatin & Transcription |
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| The EMBO Journal
(2005) 24, 358–367, doi:10.1038/sj.emboj.7600531 Published online 13 January 2005 |
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| Inducible DNA-loop formation blocks transcriptional activation by an SV40 enhancer |
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| Stefan Ludwig Ameres1, 2, Lars Drueppel2, Klaus Pfleiderer, Andreas Schmidt, Wolfgang Hillen and Christian Berens |
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Lehrstuhl für Mikrobiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany To whom correspondence should be addressed Christian Berens, Lehrstuhl für Mikrobiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Inst. für Mikrobiologie, Biochemie und Genetik, Staudtstrasse 5, 91058 Erlangen, Germany. Tel.: +49 9131 852 8802; Fax: +49 9131 852 8082; E-mail: cberens@biologie.uni-erlangen.de 1 Present address: Max F Perutz Laboratories, University Departments of the Vienna Biocenter, Department of Microbiology and Genetics, University of Vienna, Dr Bohrgasse 9/4, 1030 Vienna, Austria 2 These authors contributed equally to this work Received 18 June 2004; Accepted 3 December 2004; Published online 13 January 2005. |
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| Abstract |
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| It is well established that gene expression in eukaryotes is controlled by sequence-dependent binding of trans-acting proteins to regulatory elements like promoters, enhancers or silencers. A less well understood level of gene regulation is governed by the various structural and functional states of chromatin, which have been ascribed to changes in covalent modification of core histone proteins. And, much on how topological domains in the genome take part in establishing and maintaining distinct gene expression patterns is still unknown. Here we present a set of regulatory proteins that allow to reversibly alter the DNA structure in vivo and in vitro by adding low molecular weight effectors that control their oligomerization and DNA binding. Using this approach, we completely regulate the activity of an SV40 enhancer in HeLa cells by reversible loop formation to topologically separate it from the promoter. This result establishes a new mechanism for DNA-structure-dependent gene regulation in vivo and provides evidence supporting the structural model of insulator function. |
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| Keywords: conditional gene regulation, dimerizer, DNA-loop formation, SV40 enhancer, tet |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article (15 Jan 1998) Molecular Therapy Original Article Optimization of the Tet-On system for regulated gene expression through viral evolution Gene Therapy Original Article |
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