Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression
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The E2F transcription factor plays a pivotal role in the timely activation of gene expression during mammalian cell cycle progression, whereas pRB and related proteins control cell growth in part through the ability to block the action of E2F. To identify physiologically important E2F-responsive promoters and to study their occupancy and histone acetylation state in vivo, we have taken advantage of a cross-linking approach in synchronized, living cells. We find that the pattern of E2F and pRB-related polypeptides recruited to these promoters changes in a strikingly dynamic fashion as cells progress from quiescence into G 1 and S phase: Repression of each promoter in quiescent cells is associated with recruitment of E2F-4 and p130 and low levels of histone acetylation, but by late G 1, these proteins are replaced largely by E2F-1 and E2F-3, in concert with acetylation of histones H3 and H4 and gene activation. These findings suggest that repression and activation of E2F-responsive genes may occur through distinct E2F heterodimers that direct the sequential recruitment of enzymes able to deacetylate and then acetylate core histones.
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In G1 and quiescent cells, Rb is not detected on E2F target promoters, whereas p107 and p130 are readily detected.
“recent reports have been unable to detect Rb on E2F target promoters in G1 and quiescent cells (Rayman et al., 2002; Takahashi et al., 2000). In contrast, p107 and p130 were readily detected. While we confirm these reports”
From Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence (2003) · cites this paper as Takahashi et al., 2000
In “p130 recruitment correlates with transcriptional repression during G0 and early G1,” the paper reports strong p130 binding and no pRB binding to the promoters tested in cells reentering the cycle from quiescence. It reports only very weak p107 binding on three promoters during G0 and G1, so describing both p107 and p130 as readily detected overstates its findings. (LLM, conf=0.90)
Experimental — accuracy not yet measuredp130, rather than RB, binds to promoters of genes in G0 cells.
“Whereas p130, rather than RB, binds to the promoters of genes in G0 cells28–30”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [30]
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- Authors
- Takahashi, Y., Rayman, J. B., & Dynlacht, B. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Dynlacht, Brian David
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-04-01
- Volume
- 14
- Issue
- 7
- Pages
- 804-816
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316494
- OpenAlex
- W2147131744
- Cited by
- 621
- References
- 1
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 14 · 2020: 9 · 2019: 12 · 2018: 9 · 2017: 7 · 2016: 12 · 2015: 11 · 2014: 24 · 2013: 13 · 2012: 23
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA77245-02, R01CA077245)
- 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 › Chromatin Remodeling and Cancer
- Keywords
- E2F transcription factors, histone acetylation, histone deacetylation, transcriptional repression, transcriptional activation, cell cycle progression, G1 phase, quiescence, E2F1, E2F4, p130, histone H3 and H4 acetylation, DNA-protein crosslinks
- MeSH terms
- Binding Sites, Carrier Proteins, Cell Cycle, Chromatin, DNA-Binding Proteins, Glioblastoma, Humans, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Retinoblastoma Protein, Cell Cycle Proteins, Transcription Factor DP1, E2F Transcription Factors, E2F1 Transcription Factor, E2F3 Transcription Factor, E2F4 Transcription Factor, Retinoblastoma-Binding Protein 1
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