An embryonically expressed gene is a target for c-Myc regulation via the c-Myc-binding sequence.
We have used a subtraction/coexpression strategy involving two different tumors derived from c-myc-bearing transgenic mice to identify a gene that is a target for c-Myc regulation. The gene, expressed in certain embryonic and adult tissues and in several (but not all) c-myc-based tumors, bears a functional c-Myc-binding sequence located 3' to its transcription start site. This sequence is required for the binding of a nuclear protein complex which, by antibody analysis, includes c-Myc. This site is also required for expression of a reporter gene in chimeric constructs transfected into c-myc-overexpressing cells and, conversely, requires c-myc cotransfection for its enhanced expression in COS cells. Furthermore, transfection of c-myc blocks the normal down-regulation of this gene, which occurs in embryonic stem cells as they undergo differentiation. This target gene encodes an anonymous cDNA (ECA39) found previously to be amplified in a teratocarcinoma cell line.
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Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115.
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Kuo
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA; D004622:Embryo, Mammalian / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005786:Gene Expression Regulation; D016259:Genes, myc; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016271:Proto-Oncogene Proteins c-myc; D004247:DNA