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Molecular and Cellular Biology, May 2000, p. 3633-3639, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Complex Transcriptional Regulatory Mechanisms Control Expression of the E2F3 Locus

Monique R. Adams,dagger Rosalie Sears, Faison Nuckolls, Gustavo Leone,Dagger and Joseph R. Nevins*

Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710

Received 29 October 1999/Returned for modification 23 November 1999/Accepted 22 February 2000

E2F transcription activity has been shown to play a critical role in cell growth control, regulating the expression of a variety of genes that encode proteins important for the initiation of DNA replication and cell cycle regulation. We have shown that the E2F3 locus encodes two protein products: the E2F3a product, which is tightly regulated by cell growth, and the E2F3b product, which is constitutively expressed throughout the cell cycle. To further explore the mechanism controlling the expression of the two E2F3 gene products, we analyzed the genomic sequences flanking the 5' region of E2F3a and E2F3b. We find that a series of E2F binding sites confer negative control on the E2F3a promoter in quiescent cells, similar to the control of the E2F1 and E2F2 promoters. In addition, a group of E-box elements, which are Myc binding sites, confer responsiveness to Myc and are necessary for full activation of the E2F3a promoter in response to growth stimulation. Based on these results and past experiments, it appears that the E2F1, E2F2, and E2F3a genes are similarly regulated by growth stimulation, involving a combination of E2F-dependent negative control and Myc-mediated positive control. In contrast, the constitutive expression of the E2F3b gene more closely reflects the control of expression of the E2F4 and E2F5 genes.

* Corresponding author. Mailing address: Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2746. Fax: (919) 681-8973. E-mail: J.Nevins{at}duke.edu.

dagger Present address: Abbott Laboratories, Abbott Park, IL 60064.

Dagger Present address: Division of Human Cancer Genetics, Ohio State University, Columbus, OH 43210.

Molecular and Cellular Biology, May 2000, p. 3633-3639, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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