E2F7 represses a network of oscillating cell cycle genes to control S-phase progression
Open accessAbstract
E2F transcription factors are known to be important for timely activation of G(1)/S and G(2)/M genes required for cell cycle progression, but transcriptional mechanisms for deactivation of cell cycle-regulated genes are unknown. Here, we show that E2F7 is highly expressed during mid to late S-phase, occupies promoters of G(1)/S-regulated genes and represses their transcription. ChIP-seq analysis revealed that E2F7 binds preferentially to genomic sites containing the TTCCCGCC motif, which closely resembles the E2F consensus site. We identified 89 target genes that carry E2F7 binding sites close to the transcriptional start site and that are directly repressed by short-term induction of E2F7. Most of these target genes are known to be activated by E2Fs and are involved in DNA replication, metabolism and DNA repair. Importantly, induction of E2F7 during G(0)-G(1)/S resulted in S-phase arrest and DNA damage, whereas expression of E2F7 during G(2)/M failed to disturb cell cycle progression. These findings provide strong evidence that E2F7 directly controls the downswing of oscillating G(1)/S genes during S-phase progression.
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E2F7 encodes a transcriptional regulator of cell cycle genes.
“and encodes a transcriptional regulator of cell cycle genes,118”
From Census and evaluation of p53 target genes (2017) · cites this paper as [118]
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“We previously demonstrated strong inhibition of proliferation and induction of apoptosis for up to 4 days,(1,18) but now we induced E2F7 overexpression for up to 20 days.”
BackgroundMethodInfluentialSelf-citation
- Authors
- Westendorp, B., Mokry, M., Groot Koerkamp, M. J. A., Holstege, F. C. P., Cuppen, E., & de Bruin, A.
- Affiliations
- Utrecht University (NL)
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-12-16
- Volume
- 40
- Issue
- 8
- Pages
- 3511-3523
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3333892
- OpenAlex
- W2140037284
- Cited by
- 125
- References
- 48
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 14 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 7 · 2014: 4 · 2013: 10 · 2012: 6
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- E2F7, E2F transcription factors, transcriptional repression, S phase progression, cell cycle oscillations, DNA replication, DNA damage, S phase arrest, DNA repair, metabolic genes
- MeSH terms
- Animals, Base Sequence, Binding Sites, DNA Damage, Gene Expression Regulation, Periodicity, Repressor Proteins, Transcription, Genetic, G1 Phase, S Phase, Consensus Sequence, Genes, cdc, E2F7 Transcription Factor, Mice, Gene Regulatory Networks, S Phase Cell Cycle Checkpoints
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