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Nucleic Acids Research Advance Access originally published online on March 20, 2009
Nucleic Acids Research 2009 37(9):3007-3020; doi:10.1093/nar/gkp179
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Nucleic Acids Research, 2009, Vol. 37, No. 9 3007-3020
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gene Regulation, Chromatin and Epigenetics

Dazap2 modulates transcription driven by the Wnt effector TCF-4

Jan Lukas, Petr Mazna, Tomas Valenta, Lenka Doubravska, Vendula Pospichalova, Martina Vojtechova, Bohumil Fafilek, Robert Ivanek, Jiri Plachy, Jakub Novak and Vladimir Korinek*

Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic

*To whom correspondence should be addressed. Tel:+4202 4106 3146; Fax:+4202 4447 2282; Email: korinek{at}img.cas.cz

Received February 10, 2009. Revised February 27, 2009. Accepted March 4, 2009.

A major outcome of the canonical Wnt/β-catenin-signalling pathway is the transcriptional activation of a specific set of target genes. A typical feature of the transcriptional response induced by Wnt signalling is the involvement of Tcf/Lef factors that function in the nucleus as the principal mediators of signalling. Vertebrate Tcf/Lef proteins perform two well-characterized functions: in association with β-catenin they activate gene expression, and in the absence of Wnt ligands they bind TLE/Groucho proteins to act as transcriptional repressors. Although the general characteristics of Tcf/Lef factors are well understood, the mechanisms that control their specific roles in various cellular backgrounds are much less defined. In this report we reveal that the evolutionary conserved Dazap2 protein functions as a TCF-4 interacting partner. We demonstrate that a short region proximal to the TCF-4 HMG box mediates the interaction and that all Tcf/Lef family members associate with Dazap2. Interestingly, knockdown of Dazap2 not only reduced the activity of Wnt signalling as measured by Tcf/β-catenin reporters but additionally altered the expression of Wnt-signalling target genes. Finally, chromatin immunoprecipitation studies indicate that Dazap2 modulates the affinity of TCF-4 for its DNA-recognition motif.


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