The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer
Abstract
Many genes associated with CpG islands undergo de novo methylation in cancer. Studies have suggested that the pattern of this modification may be partially determined by an instructive mechanism that recognizes specifically marked regions of the genome. Using chromatin immunoprecipitation analysis, here we show that genes methylated in cancer cells are specifically packaged with nucleosomes containing histone H3 trimethylated on Lys27. This chromatin mark is established on these unmethylated CpG island genes early in development and then maintained in differentiated cell types by the presence of an EZH2-containing Polycomb complex. In cancer cells, as opposed to normal cells, the presence of this complex brings about the recruitment of DNA methyl transferases, leading to de novo methylation. These results suggest that tumor-specific targeting of de novo methylation is pre-programmed by an established epigenetic system that normally has a role in marking embryonic genes for repression.
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“hypermethylated regions (HyperDMRs) in HCC were enriched in the promoters of developmental genes and in genic features such as untranslated regions (UTRs) and exons (Fig. 1b and Supplementary Fig. 2f)47,48.”
From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [48]
In the citing paper
“EZH2 inhibition has been shown to augment interferoninduced gene expression in tumour cells 227-229 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [227]
In the citing paper
“Despite global DNA hypomethylation, a limited number of genomic loci gain DNA methylation during aging and in cancer.”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [47]
Citations
Cites
The fundamental role of epigenetic events in cancer
Jones, P. A., & Baylin, S. B. (2002) · Nature Reviews Genetics · doi:10.1038/nrg816 · Cited by 5,648
The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro
Reubinoff, B. E., Pera, M. F., Fong, C., Trounson, A. O., & Bongso, A. (2000) · Nature Biotechnology · doi:10.1038/74447 · Cited by 2,708
Self-citationPolycomb 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
The Polycomb group protein EZH2 directly controls DNA methylation
Viré, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., et al. (2006) · Nature · doi:10.1038/nature04431 · Cited by 2,204
The DNA methyltransferases of mammals
Bestor, T. H. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.16.2395 · Cited by 2,078
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
Role of Histone H3 Lysine 27 Methylation in X Inactivation
Plath, K., Fang, J., Mlynarczyk‐Evans, S., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., & Zhang, Y. (2003) · Science · doi:10.1126/science.1084274 · Cited by 1,241
EZH2 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
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Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061
Jones, P. A., & Baylin, S. B. (2007) · Cell · doi:10.1016/j.cell.2007.01.029 · Cited by 4,515
Esteller, M. (2008) · New England Journal of Medicine · doi:10.1056/nejmra072067 · Cited by 3,767
CpG islands and the regulation of transcription
Deaton, A. M., & Bird, A. (2011) · Genes & Development · doi:10.1101/gad.2037511 · Cited by 3,187
“Early studies suggested that CGI promoters may often lack TATA boxes and display heterogeneous TSSs (Reynolds et al. 1984).”
InfluentialA decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871
“and become de novo DNA methylated in cancer and pre-cancerous cell”
Background
Metadata
- Authors
- Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B. E., Bergman, Y., Simon, I., & Cedar, H.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Cedar, Howard
- Venue
- Nature Genetics
- Published
- 2006-12-31
- Volume
- 39
- Issue
- 2
- Pages
- 232-236
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1969670934
- Cited by
- 1,226
- References
- 31
- Citations by year
- 2026: 17 · 2025: 41 · 2024: 40 · 2023: 34 · 2022: 33 · 2021: 77 · 2020: 51 · 2019: 47 · 2018: 37 · 2017: 53 · 2016: 68 · 2015: 65 · 2014: 67 · 2013: 80 · 2012: 98
- FWCI
- 27.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Prostate Cancer Foundation
- Philip Morris International
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- Polycomb group proteins, H3K27me3, de novo methylation, CpG islands, EZH2, DNA methyltransferases, epigenetic inheritance, cancer epigenetics
- MeSH terms
- Carrier Proteins, Cells, Cultured, Colonic Neoplasms, Histones, Humans, Lysine, Methylation, Methyltransferases, Neoplasms, Viral Envelope Proteins, CpG Islands, Caco-2 Cells, DNA Methylation, Epigenesis, Genetic
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