Program in Gene Function and Expression; Program in Molecular Medicine
Medical Subject Headings
Amino Acid Sequence; Animals; Base Sequence; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic-Leucine Zipper Transcription Factors; Binding Sites; Cloning, Molecular; DNA Footprinting; DNA Primers; DNA-Binding Proteins; Deoxyribonuclease I; Dimerization; Escherichia coli; Humans; *Introns; Molecular Sequence Data; Open Reading Frames; Ornithine Decarboxylase; Polymerase Chain Reaction; Protein Multimerization; Proto-Oncogene Proteins c-myc; Rats; Recombinant Proteins; Transcription Factors
Genetics and Genomics
The oncoprotein c-Myc plays an important role in cell proliferation, transformation, inhibition of differentiation and apoptosis. These functions most likely result from the transcription factor activity of c-Myc. As a heterodimer with Max, the c-Myc protein binds to the E-box sequence (CACGTG), which is also recognized by USF dimers. In order to test differences in target gene recognition of c-Myc/Max, Max and USF dimers, we compared the DNA binding characteristics of these proteins in vitro using vaccinia viruses expressing full-length c-Myc and Max proteins. As expected, purified c-Myc/max binds specifically to a consensus E-box. The optimal conditions for DNA binding by either c-Myc/Max, Max or USF dimers differ with respect to ionic strength and Mg2+ ion concentration. Most interestingly, the c-Myc/Max complex binds with a high affinity to its natural target, the rat ODC gene, which contains two adjacent, consensus E-boxes. High affinity binding results from teh ability of c-Myc/Max dimers to bind cooperatively to these E-boxes. We propose that differential cooperative binding by E-box binding transcription factors could contribute to target gene specificity.
Rights and Permissions
Citation: Nucleic Acids Res. 1997 Apr 15;25(8):1493-501. Link to article on publisher's site
Walhout, Albertha J. M.; Gubbels, J. M.; Bernards, R.; van der Vliet, P. C.; and Timmers, H. Th. M., "c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the first intron of the rat ornithine decarboxylase (ODC) gene" (1997). Program in Gene Function and Expression Publications and Presentations. 7.