A computerized database-scan to identify c-MYC targets.
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.
Schuldiner
Oren
O
Department of Genetics, The Silberman Institute for Life Sciences, The Hebrew University, Givat-Ram, Jerusalem 91904, Israel.
Shor
Sharon
S
Benvenisty
Nissim
N
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002457:Cell Extracts; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051379:Mice; D009841:Oligonucleotides / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012984:Software
D002352:Carrier Proteins; D002457:Cell Extracts; D009841:Oligonucleotides; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins