Whole-genome analysis reveals a strong positional bias of conserved dMyc-dependent E-boxes.
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.
Hulf
Toby
T
Universität Zürich, Zoologisches Institut, Winterthurerstrasse 190, Zürich 8057, Switzerland.
Bellosta
Paola
P
Furrer
Michael
M
Steiger
Dominik
D
Svensson
David
D
Barbour
Andrew
A
Gallant
Peter
P
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D024721:E-Box Elements / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D017344:Genes, Insect / Q000235:genetics*; D016678:Genome; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102284:Myc protein, Drosophila; D014157:Transcription Factors