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

Abstract

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.

SUPPLEMENTAL MATERIAL

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

ACKNOWLEDGMENTS

We thank Eva Niederer for FACS analysis, Ruth Keist and Andrea Patrignani for help with microarrays, George Hausmann for S2 cells and an introduction to luciferase assays, and Ernst Hafen and Martin Eilers for critical reading of the manuscript.

This work was supported by grants from the Swiss National Science Foundation and the Zürcher Hochschulverein/FAN (to P.G.).