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  • The EMBO Journal (2005) 24, 358 - 367
  • doi:10.1038/sj.emboj.7600531

Published online: 13 January 2005

Inducible DNA-loop formation blocks transcriptional activation by an SV40 enhancer

Stefan Ludwig Ameres1,ab, Lars Drueppel1,b, Klaus Pfleiderer1, Andreas Schmidt1, Wolfgang Hillen1 and Christian Berens1

  1. Lehrstuhl für Mikrobiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

Correspondence to:

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

aPresent 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

bThese authors contributed equally to this work

Received 18 June 2004; Accepted 3 December 2004

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.

  • Keywords:

    • conditional gene regulation,
    • dimerizer,
    • DNA-loop formation,
    • SV40 enhancer,
    • tet