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Molecular and Cellular Biology, May 2005, p. 3411-3420, Vol. 25, No. 9
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.9.3411-3420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

cis-Regulatory Logic of Short-Range Transcriptional Repression in Drosophila melanogaster

Meghana M. Kulkarni and David N. Arnosti^*

Department of Biochemistry and Molecular Biology and Program in Genetics, Michigan State University, East Lansing, Michigan

Received 29 September 2004/ Returned for modification 8 December 2004/ Accepted 3 February 2005

Bioinformatics analysis of transcriptional control is guided by knowledge of the characteristics of cis-regulatory regions or enhancers. Features such as clustering of binding sites and co-occurrence of binding sites have aided enhancer identification, but quantitative predictions of enhancer function are not yet generally feasible. To facilitate the analysis of regulatory sequences in Drosophila melanogaster, we identified quantitative parameters that affect the activity of short-range transcriptional repressors, proteins that play key roles in development. In addition to the previously noted distance dependence, repression is strongly influenced by the stoichiometry, affinity, spacing, and arrangement of activator binding sites. Repression is insensitive to the type of activation domain, suggesting that short-range repression may primarily affect activators at the level of DNA binding. The activity of several short-range, but not long-range, repressors is circumscribed by the same quantitative parameters. This cis-regulatory "grammar" may aid the identification of enhancers regulated by short-range repressors and facilitate bioinformatic prediction of the functional output of transcriptional regulatory sequences.

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* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319. Phone: (517) 432-5504. Fax: (517) 353-9334. E-mail: arnosti{at}msu.edu.

Present address: Department of Genetics, Harvard Medical School, Boston, MA 02115-6092.

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Molecular and Cellular Biology, May 2005, p. 3411-3420, Vol. 25, No. 9
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.9.3411-3420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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