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Molecular and Cellular Biology, May 2005, p. 3401-3410, Vol. 25, No. 9
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.9.3401-3410.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Whole-Genome Analysis Reveals a Strong Positional Bias of Conserved dMyc-Dependent E-Boxes{dagger}

Toby Hulf,1 Paola Bellosta ,1,{ddagger},§ Michael Furrer,1,{ddagger} Dominik Steiger,1,{ddagger} David Svensson,2,¶ Andrew Barbour,2 and Peter Gallant1*

Zoologisches Institut,1 Institut für Mathematik, Universität Zürich, Zürich, Switzerland2

Received 3 January 2005/ Accepted 19 January 2005

Myc is a transcription factor with diverse biological effects ranging from the control of cellular proliferation and growth to the induction of apoptosis. Here we present a comprehensive analysis of the transcriptional targets of the sole Myc ortholog in Drosophila melanogaster, dMyc. We show that the genes that are down-regulated in response to dmyc inhibition are largely identical to those that are up-regulated after dMyc overexpression and that many of them play a role in growth control. The promoter regions of these targets are characterized by the presence of the E-box sequence CACGTG, a known dMyc binding site. Surprisingly, a large subgroup of (functionally related) dMyc targets contains a single E-box located within the first 100 nucleotides after the transcription start site. The relevance of this E-box and its position was confirmed by a mutational analysis of a selected dMyc target and by the observation of its evolutionary conservation in a different Drosophila species, Drosophila pseudoobscura. These observations raise the possibility that a subset of Myc targets share a distinct regulatory mechanism.

* Corresponding author. Mailing address: Universität Zürich, Zoologisches Institut, Winterthurerstrasse 190, Zürich 8057, Switzerland. Phone: 4116354812. Fax: 4116356820. E-mail: gallant{at}zool.unizh.ch.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} P.B., M.F., and D.S. contributed equally to this work.

§ Present address: Dipartimento di Scienze Mediche, Università del Piemonte Orientale "Amedeo Avogadro," 28100 Novara, Italy.

Present address: Statistical and Mathematical Science, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden.

Molecular and Cellular Biology, May 2005, p. 3401-3410, Vol. 25, No. 9
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.9.3401-3410.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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