The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
Open accessAbstract
The p16 INK4A and p14 ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood. Here, we show that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex. Significantly, EZH2 is down-regulated in stressed and senescing populations of cells, coinciding with decreased levels of associated H3K27me3, displacement of BMI1, and activation of transcription. These results provide a model for how the INK4A-ARF locus is activated and how Polycombs contribute to cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The molecular mechanisms underlying this derepression are not completely understood but have been associated with loss of polycomb group of proteins but independent of p53 (Jacobs et al., 1999; Bracken et al., 2007).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Bracken et al., 2007
In the citing paper
“During senescence, PRC delocalization from the CDKN2A locus, transcriptional downregulation of EZH2 [83], and recruitment of JMJD3 [84,85], a histone lysine demethylase that catalyzes H3K27 demethylation, lead to removal of the repressive H3K27me3 mark at the CDKN2A locus and facilitate p16 transcription.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [83]
In the citing paper
“The mechanistic details of how this happens are starting to emerge, and seem in part to involve the progressive loss of repressive Polycomb complexes 7”
From The common biology of cancer and ageing (2007) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Polycomb complexes repress developmental regulators in murine embryonic stem cells
Boyer, L. A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L. A., Lee, T. I., Levine, S. S., Wernig, M., Tajonar, A., Ray, M. K., et al. (2006) · Nature · doi:10.1038/nature04733 · Cited by 2,568
Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,296
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 1×
“SA- -gal assays were performed as previously described (Narita et al. 2003).”
MethodA gene hypermethylation profile of human cancer.
Esteller, M., Corn, P. G., Baylin, S. B., & Herman, J. G. (2001) · PubMed · Cited by 2,032
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003) · Nature · doi:10.1038/nature01587 · Cited by 1,871
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
Lessard, J., & Sauvageau, G. (2003) · Nature · doi:10.1038/nature01572 · Cited by 1,452
Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation
Molofsky, A. V., Pardal, R., Iwashita, T., Park, I.-K., Clarke, M. F., & Morrison, S. J. (2003) · Nature · doi:10.1038/nature02060 · Cited by 1,317
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsPreprint
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,286
Self-citationEZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
Bracken, A. P., Pasini, D., Capra, M., Prosperini, E., Colli, E., & Helin, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg542 · Cited by 1,196
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
The Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
Metadata
- Authors
- Bracken, A. P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Mönch, K., Minucci, S., Porse, B. T., Marine, J.-C., Hansen, K. H., & Helin, K.
- Affiliations
- University of Copenhagen (DK)
- European Institute of Oncology (IT)
- Vlaams Instituut voor Biotechnologie (BE)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-03-01
- Volume
- 21
- Issue
- 5
- Pages
- 525-530
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1820894
- OpenAlex
- W2101370480
- Cited by
- 850
- References
- 40
- Citations by year
- 2026: 16 · 2025: 14 · 2024: 20 · 2023: 26 · 2022: 29 · 2021: 40 · 2020: 43 · 2019: 30 · 2018: 32 · 2017: 50 · 2016: 76 · 2015: 48 · 2014: 48 · 2013: 55 · 2012: 58
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Kræftens Bekæmpelse
- Sundhed og Sygdom, Det Frie Forskningsråd
- Lundbeckfonden (R9-2007-978)
- Novo Nordisk
- Novo Nordisk Fonden
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Polycomb group proteins, INK4a/ARF locus, p16INK4a, p14ARF, cellular senescence, BMI1, EZH2, polycomb repressive complex 2, H3K27me3, chromatin repression, transcriptional activation, cancer
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Animals, Cell Line, DNA-Binding Proteins, Embryo, Mammalian, Fibroblasts, Histones, Humans, Methylation, Mice, Inbred C57BL, Neoplasms, Nuclear Proteins, Histone-Lysine N-Methyltransferase, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Stem Cells, Transcription Factors, Down-Regulation, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Genes, p16, Oligonucleotide Array Sequence Analysis, Tumor Suppressor Protein p14ARF, Chromatin Immunoprecipitation, Mice, Polycomb Repressive Complex 1, Polycomb Repressive Complex 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
