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. 1997 Apr 15;25(8):1516–1525. doi: 10.1093/nar/25.8.1516

c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the first intron of the rat ornithine decarboxylase (ODC) gene

AJM Walhout 1, JM Gubbels 1, R Bernards 1, van der Vliet PC 1, HTM Timmers 1
PMCID: PMC146634  PMID: 9106360

Abstract

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 the 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.

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Selected References

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