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Molecular and Cellular Biology, December 2005, p. 10433-10441, Vol. 25, No. 23
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.23.10433-10441.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hairless-Mediated Repression of Notch Target Genes Requires the Combined Activity of Groucho and CtBP Corepressors

Anja C. Nagel,1 Alena Krejci,2 Gennady Tenin,1 Alejandro Bravo-Patiño,1,{dagger} Sarah Bray,2 Dieter Maier,1 and Anette Preiss1*

Institut für Genetik (240), Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany,1 Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, United Kingdom2

Received 31 May 2005/ Returned for modification 28 July 2005/ Accepted 14 September 2005

Notch signal transduction centers on a conserved DNA-binding protein called Suppressor of Hairless [Su(H)] in Drosophila species. In the absence of Notch activation, target genes are repressed by Su(H) acting in conjunction with a partner, Hairless, which contains binding motifs for two global corepressors, CtBP and Groucho (Gro). Usually these corepressors are thought to act via different mechanisms; complexed with other transcriptional regulators, they function independently and/or redundantly. Here we have investigated the requirement for Gro and CtBP in Hairless-mediated repression. Unexpectedly, we find that mutations inactivating one or the other binding motif can have detrimental effects on Hairless similar to those of mutations that inactivate both motifs. These results argue that recruitment of one or the other corepressor is not sufficient to confer repression in the context of the Hairless-Su(H) complex; Gro and CtBP need to function in combination. In addition, we demonstrate that Hairless has a second mode of repression that antagonizes Notch intracellular domain and is independent of Gro or CtBP binding.

* Corresponding author. Mailing address: Anette Preiss, Institut für Genetik (240), Universität Hohenheim, Garbenstr. 30, D-70599 Stuttgart, Germany. Phone: 49 711 459 2206. Fax: 49 711 459 2211. E-mail: preiss{at}uni-hohenheim.de.

{dagger} Present address: Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, CMEB, 58262 Morelia, Mich., Mexico.

Molecular and Cellular Biology, December 2005, p. 10433-10441, Vol. 25, No. 23
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.23.10433-10441.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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