E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression

  • Ingrid Thurlings
  • Alain de BruinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1342)


Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growth and DNA metabolism, respectively. These findings provided the first clues that the E2F transcription factor might be an important regulator of the cell cycle. Since this initial discovery in 1987, several additional E2F family members have been identified, and more than 100 targets genes have been shown to be directly regulated by E2Fs, the majority of these are important for controlling the cell cycle.

The progression of a cell through the cell cycle is accompanied with the increased expression of a specific set of genes during one phase of the cell cycle and the decrease of the same set of genes during a later phase of the cell cycle. This roller coaster ride, or oscillation, of gene expression is essential for the proper progression through the cell cycle to allow accurate DNA replication and cell division. The E2F transcription factors have been shown to be critical for the temporal expression of the oscillating cell cycle genes.

This review will focus on how the oscillation of E2Fs and their targets is regulated by transcriptional, post-transcriptional and post-translational mechanism in mammals, yeast, flies, and worms. Furthermore, we will discuss the functional impact of E2Fs on the cell cycle progression and outline the consequences when E2F expression is disturbed.

Key words

E2F transcription factors Cell cycle Oscillation Gene expression RB/E2F pathway 



We thank B. Westendorp and W.J. Bakker for critically reviewing the manuscript.


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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pathobiology, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
  2. 2.Division of Molecular Genetics, Department of PediatricsUniversity Medical Center GroningenGroningenThe Netherlands

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