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Molecular and Cellular Biology, May 2004, p. 4341-4350, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4341-4350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Groucho Oligomerization Is Required for Repression In Vivo

Haiyun Song,1 Peleg Hasson,2 Ze’ev Paroush,2 and Albert J. Courey1*

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569,1 Department of Biochemistry, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel2

Received 19 October 2003/ Returned for modification 22 December 2003/ Accepted 11 February 2004

Drosophila Groucho (Gro) is a member of a family of metazoan corepressors with widespread roles in development. Previous studies indicated that a conserved domain in Gro, termed the Q domain, was required for repression in cultured cells and mediated homotetramerization. Evidence presented here suggests that the Q domain contains two coiled-coil motifs required for oligomerization and repression in vivo. Mutagenesis of the putative hydrophobic faces of these motifs, but not of the hydrophilic faces, prevents the formation of both tetramers and higher order oligomers. Mutagenesis of the hydrophobic faces of both coiled-coil motifs in the context of a Gal4-Gro fusion protein prevents repression of a Gal4-responsive reporter in S2 cells, while mutagenesis of a single motif weakens repression. The finding that the repression directed by the single mutants depends on endogenous wild-type Gro further supports the idea that oligomerization plays a role in repression. Overexpression in the fly of forms of Gro able to oligomerize, but not of a form of Gro unable to oligomerize, results in developmental defects and ectopic repression of Gro target genes in the wing disk. Although the function of several corepressors is suspected to involve oligomerization, these studies represent one of the first direct links between corepressor oligomerization and repression in vivo.


* Corresponding author. Mailing address: Department of Chemistry and Biochemistry, UCLA, 607 Charles E. Young Drive, East, Box 951569, Los Angeles, CA 90095-1569. Phone: (310) 825-2530. Fax: (310) 206-4038. E-mail: courey{at}chem.ucla.edu.


Molecular and Cellular Biology, May 2004, p. 4341-4350, Vol. 24, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.10.4341-4350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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