A Common Set of Gene Regulatory Networks Links Metabolism and Growth Inhibition
Open accessAbstract
Using genome-wide analysis of transcription factor occupancy, we investigated the mechanisms underlying three mammalian growth arrest pathways that require the pRB tumor suppressor family. We found that p130 and E2F4 cooperatively repress a common set of genes under each growth arrest condition and showed that growth arrest is achieved through repression of a core set of genes involved not only in cell cycle control but also mitochondrial biogenesis and metabolism. Motif-finding algorithms predicted the existence of nuclear respiratory factor-1 (NRF1) binding sites in E2F target promoters, and genome-wide factor binding analysis confirmed our predictions. We showed that NRF1, a factor known to regulate expression of genes involved in mitochondrial function, is a coregulator of a large number of E2F target genes. Our studies provide insights into E2F regulatory circuitry, suggest how factor occupancy can predict the expression signature of a given target gene, and reveal pathways deregulated in human tumors.
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Previous attempts to detect RB bound to specific E2F target promoters in growing or quiescent cells failed or gave contrasting results.
“Previous attempts to detect RB bound to specific E2F target promoters in growing or quiescent cells have failed or yielded contrasting results (Cam et al., 2004; Rayman et al., 2002; Wells et al., 2000)”
From Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence (2010) · cites this paper as Cam et al., 2004
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References 41 · Cited by 322
Research works printed but not linked: 1
- Kelly, D.P., and Scarpulla, R.C. (2004). Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Virbasius, J.V., and Scarpulla, R.C. (1994). Activation of the human Dev. 18, 357-368. mitochondrial transcription factor A gene by nuclear respiratory fac- tors: a potential regulatory link between nuclear and mitochondrial Lee, E.Y., Cam, H., Ziebold, U., Rayman, J.B., Lees, J.A., and Dyn- gene expression in organelle biogenesis. Proc. Natl. Acad. Sci. USA
- Authors
- Cam, H., Balciunaite, E., Blais, A., Spektor, A., Scarpulla, R. C., Young, R., Kluger, Y., & Dynlacht, B. D.
- Affiliations
- New York University (US)
- Northwestern Medicine (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Dynlacht, Brian David
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 16
- Issue
- 3
- Pages
- 399-411
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2084544581
- Cited by
- 322
- References
- 41
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 11 · 2022: 12 · 2021: 12 · 2020: 7 · 2019: 2 · 2018: 12 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 7 · 2013: 21 · 2012: 17
- FWCI
- 13.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Cancer Institute (R01CA077245, 2R01 CA77245-07)
- 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
- gene regulatory networks, growth arrest, p130, E2F4, transcription factor occupancy, NRF1, mitochondrial biogenesis, cellular metabolism, cell cycle regulation, transcriptional repression, E2F target genes, tumor suppressor pathways
- MeSH terms
- Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, Genes, Regulator, Humans, Neoplasms, Nuclear Proteins, Proteins, Transcription Factors, Tumor Cells, Cultured, Apoptosis, Oligonucleotide Array Sequence Analysis, Amino Acid Motifs, Gene Expression Profiling, E2F4 Transcription Factor, Retinoblastoma-Like Protein p130, Retinoblastoma-Like Protein p107, Nuclear Respiratory Factor 1
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