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Molecular and Cellular Biology, January 1999, p. 690-703, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Characterization of the DNA-Binding and Dimerization Properties of the Nuclear Orphan Receptor Germ Cell Nuclear Factor

Holger Greschik,1 Jean-Marie Wurtz,2 Philip Hublitz,1 Fabian Köhler,1 Dino Moras,2 and Roland Schüle1,*

Institut für Experimentelle Krebsforschung, Klinik für Tumorbiologie an der Universität Freiburg, D-79106 Freiburg, Germany,1 and Institut de Genetique et de Biologie Moleculaire et Cellulaire, CU de Strasbourg, 67404 Illkirch Cedex, France2

Received 13 July 1998/Returned for modification 17 August 1998/Accepted 19 October 1998

The orphan receptor germ cell nuclear factor (GCNF) is a member of the superfamily of nuclear receptors. During development, GCNF exhibits a restricted brain-specific expression pattern, whereas GCNF expression in the adult is germ cell specific. Therefore, the receptor may participate in the regulation of neurogenesis and reproductive functions. No natural GCNF target gene has yet been identified, but recent data demonstrate specific and high-affinity binding of GCNF either to the direct repeat DNA element AGGTCAAGGTCA (DR0) or to extended half-sites, such as TCAAGGTCA. In this study, we show that murine GCNF (mGCNF) can bind as a homodimer to extended half-sites, thus describing a novel property within the nuclear receptor superfamily. Homodimeric binding to extended half-sites requires the presence of a dimerization function within the mGCNF DNA-binding domain (DBD) and a novel dimerization surface encompassing the putative helix 3 and the helix 12 region of the mGCNF ligand-binding domain (LBD). In addition, the mGCNF LBD has the potential to adopt different conformations with distinct dimerization properties. The helix 12 region of the mGCNF LBD not only regulates the switch between these dimerization conformations but also dictates the DNA-binding behavior and transcriptional properties of the different dimerization conformations. In summary, our findings describe unique DNA-binding and dimerization properties of a nuclear receptor and suggest a novel mechanism that allows mGCNF to modulate target gene activity.

* Corresponding author. Mailing address: Institut für Experimentelle Krebsforschung, Klinik für Tumorbiologie an der Universität Freiburg, Breisacherstrasse 117, D-79106 Freiburg, Germany. Phone: 49-761-206-1510. Fax: 49-761-206-1508. E-mail: schuele{at}tumorbio.uni-freiburg.de.

Molecular and Cellular Biology, January 1999, p. 690-703, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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