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J. Biol. Chem., Vol. 279, Issue 48, 50358-50365, November 26, 2004

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Interaction, Cooperative Promoter Modulation, and Renal Colocalization of GCMa and Pitx2^*

Steffen W. Schubert, Elena Kardash, Muhammad Amir Khan, Tatiana Cheusova, Karin Kilian, Michael Wegner, and Said Hashemolhosseini

From the Institut für Biochemie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany

The transcription factor GCMa is a member of a new small family of transcription factors with a conserved zinc-containing DNA-binding domain. All members of this transcription factor family play crucial roles as master regulators during development. GCMa is restricted to placenta during development and to kidney and thymus at postnatal stages. It is essential for the formation of the placental labyrinth and as a consequence for survival of the embryo from mid-embryogenesis onwards. Here, we identify Pitx transcription factors as GCMa-interacting proteins. We show that Pitx proteins interact via their conserved homeodomain with the DNA-binding domain of GCMa. As a consequence, Pitx proteins and GCMa exhibit cooperative DNA binding. Furthermore, Pitx proteins influence GCMa-dependent promoter activation in a cell-specific manner. One of the three Pitx paralogues in mice, Pitx2, is the predominant Pitx member present in the placenta and colocalizes on the cellular level with GCMa in the kidney. This is the first description of a regulatory cross-talk between a transcription factor of the GCM family and a homeodomain protein.

Received for publication, April 26, 2004 , and in revised form, September 2, 2004.

^* This work was supported by the Deutsche Forschungsgemeinschaft (Grant SFB473 to S. H. and M. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

To whom correspondence should be addressed. Tel.: 49-9131-85-24634; Fax: 49-9131-85-22484; E-mail: sh{at}biochem.uni-erlangen.de.

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