The c-MYC oncogene plays a pivotal role in the malignant transformation of various types of human cancer. It is also a key regulator of cellular proliferation, embryonic differentiation and apoptosis. c-MYC encodes a transcription factor that activates target genes in a sequence specific manner through heterodimerization with the ubiquitously expressed factor MAX. Identifying c-MYC target genes is therefore crucial for elucidating the molecular pathways that are downstream of MYC. Most of the c-MYC targets isolated to date as well as targets of other transcription factors have been identified by differential expression or the candidate gene approach. In this paper, we outline a computer-based scan that allows us to create a pool of putative target genes for a transcription factor. The scan is based on a set of criteria including sequence specificity of the c-MYC transcription factor, sequence location and evolutionary conservation of these regulatory elements. Using this procedure, we have identified 12 putative targets for c-MYC. Expression analyses, DNA binding assays and chimeric promoter-reporter experiments suggest that two genes, NM23-H2 and N-RAS, may indeed be direct targets for c-MYC activation. This type of computer-based scan may have a general use to identify targets for other transcription factors.
Bibliographical noteFunding Information:
We thank Dr Lukas Kuhn for the IRP1 probe, Dr Thomas Broun for the FGF6 probe, Dr Craig Hauser for the HOX2.1 probe, Dr Matthias Engel and Dr Welter for the NM23-H1 and H2 probes, Dr Angel Pellicer for the N-RAS probe, Dr Baruch Kanner for the GAT1 probe, Dr Harry Iland for N-RAS-CAT constructs and Dr Jerry Lingrel for the ATPα1 probe. We thank the members of our laboratory for their critical reading of the manuscript. This research was supported by grant #98-00074 from the United States–Israel Bi-national Science Foundation (BSF), Jerusalem, Israel and by a grant from the Israel Cancer Research Fund. O.S. is a Clore fellow.
- DNA binding site
- Transcription factor