Target Gene Specificity of E2F and Pocket Protein Family Members in Living Cells

doi:10.1128/MCB.20.16.5797-5807.2000

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Molecular and Cellular Biology, August 2000, p. 5797-5807, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Target Gene Specificity of E2F and Pocket Protein Family Members in Living Cells

Julie Wells, Kathryn E. Boyd, Christopher J. Fry, Stephanie M. Bartley, and Peggy J. Farnham^*

McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706

Received 30 November 1999/Returned for modification 19 January 2000/Accepted 6 May 2000

E2F-mediated transcription is thought to involve binding of an E2F-pocket protein complex to promoters in the G₀ phase ofthe cell cycle and release of the pocket protein in late G₁, followedby release of E2F in S phase. We have tested this model by monitoringprotein-DNA interactions in living cells using a formaldehydecross-linking and immunoprecipitation assay. We find that E2Ftarget genes are bound by distinct E2F-pocket protein complexeswhich change as cells progress through the cell cycle. We alsofind that certain E2F target gene promoters are bound by pocketproteins when such promoters are transcriptionally active. Ourdata indicate that the current model applies only to certain E2Ftarget genes and suggest that Rb family members may regulate transcriptionin both G₀ and S phases. Finally, we find that a given promotercan be bound by one of several different E2F-pocket protein complexesat a given time in the cell cycle, suggesting that cell cycle-regulatedtranscription is a stochastic, not a predetermined,process.

^* Corresponding author. Mailing address: McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison,WI 53706. Phone: (608) 262-2071. Fax: (608) 262-2824. E-mail:farnham{at}oncology.wisc.edu.

Present address: Department of Pathology, Yale University School of Medicine, New Haven, CT06520.

Present address: Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester, MA01605.

Molecular and Cellular Biology, August 2000, p. 5797-5807, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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