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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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Charting the dynamic epigenome during B-cell development
Martín-Subero, J. I., & Oakes, C. C. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.08.008 · Cited by 41
Blancafort, P., Jin, J. J., & Frye, S. V. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.080697 · Cited by 34
“Multiple groups had proposed that in cancer cells H3K27me3 could mark genes subsequently silenced by DNAme, although many developmentally regulated genes are marked H3K27me3 in the absence of DNAme (Ohm et al., 2007; Schlesinger et al., 2007;Widschwendter et al., 2007).”
BackgroundYamashita, S., Nanjo, S., Rehnberg, E., Iida, N., Takeshima, H., Ando, T., Maekita, T., Sugiyama, T., & Ushijima, T. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0789-8 · Cited by 34
Carlier, F., Li, M., Maroc, L., Debuchy, R., Souaid, C., Noordermeer, D., Grognet, P., & Malagnac, F. (2021) · Epigenetics & Chromatin · doi:10.1186/s13072-021-00395-7 · Cited by 32
Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy
Sandi, C., Al‐Mahdawi, S., & Pook, M. A. (2013) · Genetics Research International · doi:10.1155/2013/852080 · Cited by 38
“In addition, genome-wide studies in cancer cells have highlighted the fact that the genes that are already silenced by Polycomb complexes are more susceptible to DNA methylation compared to other genes ([33, 34], reviewed in [35]).”
BackgroundFOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis
Levanon, K., Sapoznik, S., Bahar‐Shany, K., Brand, H., Shapira‐Frommer, R., Korach, J., Hirsch, M. S., Roh, M. H., Miron, A., Liu, J. F., et al. (2013) · Oncogene · doi:10.1038/onc.2013.394 · Cited by 34
Chromatin‐modifying proteins in cancer
Fog, C. K., Jensen, K. T., & Lund, A. H. (2007) · Apmis · doi:10.1111/j.1600-0463.2007.apm_776.xml.x · Cited by 35
Gebhard, C., Glatz, D., Schwarzfischer, L., Wimmer, J., Stasik, S., Nuetzel, M., Heudobler, D., Andreesen, R., Ehninger, G., Thiede, C., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0165-2 · Cited by 34
“methylated in cancer are targets of PcG repression and marked by histone H3 lysine 27 trimethylation (H3K27me3) in embryonic stem cells [36].”
BackgroundRecent advances of histone modification in gastric cancer
Zhen, T.-M., Yang, W.-Y., & Gu, J.-L. (2014) · Journal of Cancer Research and Therapeutics · doi:10.4103/0973-1482.151450 · Cited by 33
Structural biology-based insights into combinatorial readout and crosstalk among epigenetic marks
Du, J., & Patel, D. J. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.04.011 · Cited by 32
“Different from normal cells, the polycomb complex of cancer cells can both establish the H3K27me3 mark and recruit the DNA methyltransferase, with the latter resulting in de novo DNA methylation at certain regions [59].”
BackgroundCREB engages C/EBPδ to initiate leukemogenesis
Tregnago, C., Manara, E., Zampini, M., Bisio, V., Borga, C., Bresolin, S., Aveic, S., Germanò, G., Basso, G., & Pigazzi, M. (2016) · Leukemia · doi:10.1038/leu.2016.98 · Cited by 33
Oittinen, M., Popp, A., Kurppa, K., Lindfors, K., Mäki, M., Kaikkonen, M. U., & Viiri, K. M. (2016) · Stem Cells · doi:10.1002/stem.2479 · Cited by 33
Enhancer of Zeste Homolog 2 in Colorectal Cancer Development and Progression
Bremer, S. C. B., Conradi, L., Mechie, N.-C., Amanzada, A., Mavropoulou, E., Kitz, J., Ghadimi, M. B., Ellenrieder, V., Ströbel, P., Heßmann, E., et al. (2019) · Digestion · doi:10.1159/000504093 · Cited by 33
Principles of Epigenetic Homeostasis Shared Between Flowering Plants and Mammals
Williams, B. P., & Gehring, M. A. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.06.019 · Cited by 35
Li, J., Pinto‐Duarte, A., Zander, M., Cuoco, M. S., Lai, C.-Y., Osteen, J. K., Fang, L., Luo, C., Lucero, J. D., Castanon, R., et al. (2022) · eLife · doi:10.7554/elife.66909 · Cited by 40
De Novo DNA Methyltransferase DNMT3b Interacts with NEDD8-modified Proteins
Shamay, M., Greenway, M., Liao, G., Ambinder, R. F., & Hayward, S. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.155721 · Cited by 32
Funata, S., Matsusaka, K., Yamanaka, R., Yamamoto, S., Okabe, A., Fukuyo, M., Aburatani, H., Fukayama, M., & Kaneda, A. (2017) · Oncotarget · doi:10.18632/oncotarget.19423 · Cited by 33
“The polycomb repressive complex, for example, establishes and maintains H3K27me3 marks, which were suggested to be pre-marks for de novo DNA hypermethylation [29–32].”
Fuse-binding protein 1 is a target of the EZH2 inhibitor GSK343, in osteosarcoma cells
Xiong, X., Zhang, J.-L., Liang, W., Cao, W., Qin, S., Dai, L., Ye, D., & Liu, Z. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3541 · Cited by 32
Severson, P. L., Tokar, E. J., Vrba, L., Waalkes, M. P., & Futscher, B. (2012) · Epigenetics · doi:10.4161/epi.22163 · Cited by 33
Takeshima, H., Ikegami, D., Wakabayashi, M., Niwa, T., Kim, Y.-J., & Ushijima, T. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs294 · Cited by 32
The multi-omic landscape of transcription factor inactivation in cancer
Teschendorff, A. E., Zheng, S., Feber, A., Yang, Z., Beck, S., & Widschwendter, M. (2016) · Genome Medicine · doi:10.1186/s13073-016-0342-8 · Cited by 30
“often mark transcription factors that are needed for development and differentiation [10, 11], are significantly more likely to be hypermethylated in cancer [4, 5, 12] and aged normal tissue [13–15] compared with random gene sets.”
BackgroundResultInsight into origins, mechanisms, and utility of DNA methylation in B-cell malignancies
Oakes, C. C., & Martín-Subero, J. I. (2018) · Blood · doi:10.1182/blood-2018-02-692970 · Cited by 33
DNA methylation correlates of chronological age in diverse human tissue types
Jain, N., Li, J., Lin, T., Jasmine, F., Kibriya, M. G., Demanelis, K., Oliva, M., Chen, L., & Pierce, B. L. (2024) · Epigenetics & Chromatin · doi:10.1186/s13072-024-00546-6 · Cited by 33
Epigenetic silencing ofNTSR1is associated with lateral and noninvasive growth of colorectal tumors
Kamimae, S., Yamamoto, E., Kai, M., Niinuma, T., Yamano, H.-O., Nojima, M., Yoshikawa, K., Kimura, T., Takagi, R., Harada, E., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5034 · Cited by 34
Smith, E. N., Ghia, E. M., DeBoever, C., Rassenti, L. Z., Jepsen, K., Yoon, K.-A., Matsui, H., Rozenzhak, S., Alakus, H., Shepard, P. J., et al. (2015) · Blood Cancer Journal · doi:10.1038/bcj.2015.14 · Cited by 33
Shen, C., Huang, Y., Liu, Y., Wang, G., Zhao, Y., Wang, Z. P., Teng, M., Wang, Y., Flockhart, D. A., Skaar, T. C., et al. (2011) · BMC Systems Biology · doi:10.1186/1752-0509-5-67 · Cited by 31
“Although tumorigenic gene silencing mediated by H3K27me3 has been shown to occur in the absence of DNA methylation [38,39], repressive histone marks frequently coordinate with the more permanent mark of DNA methylation in heterochromatin [39-41].”
BackgroundStem Cell Plasticity in Development and Cancer: Epigenetic Origin of Cancer Stem Cells
Shah, M., & Allegrucci, C. (2012) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-4525-4_24 · Cited by 33
Nishioka, C., Ikezoe, T., Yang, J., Udaka, K., & Yokoyama, A. (2011) · Blood Cancer Journal · doi:10.1038/bcj.2011.33 · Cited by 31
Wong, C., Wong, C. C., Ng, Y., Au, S. L., Ko, F. C. F., & Ng, I. O. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016702 · Cited by 31
“More recently, significant enrichment of H3K27 methylation has been found in hypermethylated genes in human cancers and implicated in de novo DNA methylation [40,41,42].”
BackgroundRibarska, T., Bastian, K.-M., Koch, A., & Schulz, W. A. (2012) · Asian Journal of Andrology · doi:10.1038/aja.2011.160 · Cited by 31
Hypermethylation of the Polycomb Group Target Gene PCDH7 in Bladder Tumors from Patients of All Ages
Beukers, W., Hercegovac, A., Vermeij, M., Kandimalla, R., Blok, A. C., van der Aa, M. N. M., Zwarthoff, E. C., & Zuiverloon, T. C. M. (2013) · The Journal of Urology · doi:10.1016/j.juro.2013.01.078 · Cited by 31
“Previous studies have reported polycomb group (PcG) target genes to be more frequent targets of aberrant silencing by DNA methylation than non-PcG target genes.(11-13) These genes are targets for PcG complexes, which are the determining factor in cell lineage choices during”
BackgroundPharmacologic down-regulation of EZH2 suppresses bladder cancerin vitroandin vivo
Tang, S., Huang, H., Wu, H.-U., Tsai, Y.-T., Chuang, M., Yu, C., Huang, S.-M., Sun, G.-H., Chang, S.-Y., Hsiao, P., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1867 · Cited by 31
“A remarkable link between EZH2 binding and the aberrant methylation of CpG islands at promoters had been shown in different cancers [34-36].”
BackgroundH3K4 Acetylation, H3K9 Acetylation and H3K27 Methylation in Breast Tumor Molecular Subtypes
Judes, G., Dagdemir, A., Karslı-Çeppioğlu, S., Lebert, A., Echegut, M., Ngollo, M., Bignon, Y., Penault-Llorca, F. M., & Bernard-Gallon, D. J. (2016) · Epigenomics · doi:10.2217/epi-2016-0015 · Cited by 31
Deshmukh, A. P., Arfuso, F., Newsholme, P., & Dharmarajan, A. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.01.016 · Cited by 31
EZH2: novel therapeutic target for human cancer
Li, L. (2014) · Biomedicine · doi:10.7603/s40681-014-0001-6 · Cited by 30
Replication stress, a source of epigenetic aberrations in cancer?
Jasencakova, Z., & Groth, A. (2010) · BioEssays · doi:10.1002/bies.201000055 · Cited by 29
Drug targeting of NR4A nuclear receptors for treatment of acute myeloid leukemia
Boudreaux, S. P., Duren, R. P., Call, S. G., Nguyen, L., Freire, P. R., Narayanan, P., Redell, M. S., & Conneely, O. M. (2018) · Leukemia · doi:10.1038/s41375-018-0174-1 · Cited by 33
Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression
Xu, J., Shi, J., Cui, X., Cui, Y., Li, J. J., Goel, A., Chen, X., Issa, J. J., Su, J., & Li, W. (2021) · Nature Communications · doi:10.1038/s41467-020-20492-7 · Cited by 31
Lin, H., Hung, S., Lee, M., Chiou, W., Huang, T., Tseng, C.-E., Shih, L.-Y., Lin, R.-I., Lin, J. M. J., Lai, Y.-H., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2821 · Cited by 31
“com/oncotarget demonstrated that EZH2-mediated H3K27me3 correlates tightly with DNA methylation [11, 21-22] or at least in a regional-dependent manner [23].”
BackgroundHäfner, N., Diebolder, H., Jansen, L., Hoppe, I., Dürst, M., & Runnebaum, I. B. (2010) · Gynecologic Oncology · doi:10.1016/j.ygyno.2010.11.018 · Cited by 30
Aberrant Epigenetic Silencing of Tumor Suppressor Genes Is Reversed by Direct Reprogramming
Ron-Bigger, S., Bar‐Nur, O., Isaac, S., Bocker, M., Lyko, F., & Eden, A. (2010) · Stem Cells · doi:10.1002/stem.468 · Cited by 30
Alterations of Epigenetic Regulators in Pancreatic Cancer and Their Clinical Implications
Silverman, B., & Shi, J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122138 · Cited by 32
“At early stage of definitive endoderm differentiation, KDM6A/B demethylate H3K27me3 which leads to upregulation of WNT3 expression and activation of WNT signaling pathway, which further promotes mesendoderm differentiation.”
BackgroundInfluentialAberrant expression of DPPA2 and HIWI genes in colorectal cancer and their impacts on poor prognosis
Raeisossadati, R., Abbaszadegan, M. R., Moghbeli, M., Tavassoli, A., Kihara, A. H., & Forghanifard, M. M. (2014) · Tumor Biology · doi:10.1007/s13277-014-1690-x · Cited by 29
“Stem and cancer cells as well as germ cells share a common subpopulation of expressed genes in biological processes such as proliferation and selfrenewal [31, 32].”
BackgroundPolycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation
Thornton, S. R., Butty, V. L., Levine, S. S., & Boyer, L. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110498 · Cited by 28
“For example, PRC2 target genes in ESCs are more likely to show promoter DNA hypermethylation in cancer cells, suggesting that H2K27me3 marks genes that become targets for more permanent silencing [48–51].”
BackgroundEvidence for Converging DNA Methylation Pathways in Placenta and Cancer
Lorincz, M. C., & Schübeler, D. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.10.009 · Cited by 28
Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation
Patani, H., Rushton, M. D., Higham, J., Álvarez–Teijeiro, S., Oxley, D., Cutillas, P. R., Sproul, D., & Ficz, G. (2020) · Nature Communications · doi:10.1038/s41467-020-17269-3 · Cited by 29
Chromatin Mechanisms Regulating Gene Expression in Health and Disease
Bonifer, C., & Cockerill, P. N. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-8216-2_2 · Cited by 30
Down-regulation of Cdx2 in colorectal carcinoma cells by the Raf–MEK–ERK 1/2 pathway
Krueger, F., Madeja, Z. E., Hemberger, M., McMahon, M., Cook, S. J., & Gaunt, S. J. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.07.020 · Cited by 29
DNA methylation and demethylation probed by small molecules
Szyf, M. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2010.09.002 · Cited by 31
BRAF mutation-specific promoter methylation of FOX genes in colorectal cancer
Roon, E. H. J. V., Boot, A., Dihal, A. A., Ernst, R. F., van Wezel, T., Morreau, H. M., & Boer, J. M. (2013) · Clinical Epigenetics · doi:10.1186/1868-7083-5-2 · Cited by 31
“These studies led to the suggestion that colon cancer cells utilize a pre-existing repression program to target loci for cancer-specific promoter methylation [16,18-20].”
Reduced-representation methylation mapping
Jeddeloh, J. A., Greally, J. M., & Rando, O. J. (2008) · Genome biology · doi:10.1186/gb-2008-9-8-231 · Cited by 29
“Intriguingly, a specific subset of CG-dense promoters tended to be more consistently susceptible to this acquisition of methylation, an observation paralleling changes observed in cancer cells [26].”
ResultApplication of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia
Zhang, Z., Huang, J., Zhang, Z., Shen, H., Tang, X., Wu, D., Bao, X., Xu, G., & Chen, S. (2024) · Biomarker Research · doi:10.1186/s40364-024-00600-1 · Cited by 30
Rönsch, K., Jäger, M., Schöpflin, A., Danciu, M., Laßmann, S., & Hecht, A. (2011) · Epigenetics · doi:10.4161/epi.6.5.15300 · Cited by 28
Epigenetic regulation leading to induced pluripotency drives cancer development in vivo
Ohnishi, K., Semi, K., & Yamada, Y. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.07.020 · Cited by 27
Antonelli, M., Fadda, A., Loi, E., Moi, L., Zavattari, C., Sulas, P., Gentilini, D., Cameli, C., Bacchelli, E., Badiali, M., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24480 · Cited by 28
Beetch, M., Boycott, C., Harandi‐Zadeh, S., Yang, T., Martin, B. J. E., Dixon-McDougall, T., Ren, K., Gacad, A., Dupuis, J. H., Ullmer, M., et al. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108815 · Cited by 28
Role of Gene Methylation in Antitumor Immune Response: Implication for Tumor Progression
Serrano, A., Castro-Vega, I., & Redondo, M. (2011) · Cancers · doi:10.3390/cancers3021672 · Cited by 28
Pisanic, T. R., Athamanolap, P., & Wang, T. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.08.030 · Cited by 27
Modulation of Cellular CpG DNA Methylation by Kaposi's Sarcoma-Associated Herpesvirus
Journo, G., Tushinsky, C., Shterngas, A., Avital, N., Eran, Y., Karpuj, M. V., Frenkel‐Morgenstern, M., & Shamay, M. (2018) · Journal of Virology · doi:10.1128/jvi.00008-18 · Cited by 28
“The KSHV-encoded microRNA, miR-K12-4-5p, targets Rbl2, the negative regulator of DNMTs, leading to increased levels of DNMT3a and, to a lesser extent, DNMT1 and DNMT3b (16).”
BackgroundYoo, E. J., Park, S.-Y., Cho, N., Kim, N., Lee, H. S., & Kang, G. H. (2008) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-008-0596-7 · Cited by 27
“Although we could not explore the PRC occupancy of the examined 25 genes in gastric epithelial stem cells, published information about the occupancy by Polycomb group components (Suz12 and Eed) or H3K27 trimethylation at the genes in ES cells enabled us to analyze the association [23].”
BackgroundInfluentialHuang, Y., Yang, Q., Zheng, Y., Lin, L., Xu, X., Xu, X., Silva, T. C., Hazawa, M., Peng, L., Cao, H., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab679 · Cited by 26
Starlard‐Davenport, A., Tryndyak, V., James, S. R., Karpf, A. R., Latendresse, J. R., Beland, F. A., & Pogribny, I. P. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp304 · Cited by 27
The Importance Of Epigenetic Alterations In The Development Of Epstein-Barr Virus-Related Lymphomas
Takács, M., Segesdi, J., Bánáti, F., Koroknai, A., Wolf, H. J., Niller, H. H., & Minárovits, J. (2009) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2009.012 · Cited by 27
Hsp90 as a “Chaperone” of the Epigenome
Isaacs, J. S. (2015) · Advances in cancer research · doi:10.1016/bs.acr.2015.09.003 · Cited by 28
Momparler, R. L., Côté, S., Momparler, L. F., & Idaghdour, Y. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00019 · Cited by 27
Bonifer, C., & Bowen, D. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001377 · Cited by 26
Kron, K. J., Trudel, D., Pethe, V. V., Briollais, L., Fleshner, N. E., van der Kwast, T., & Bapat, B. V. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3139 · Cited by 26
“This phenomenon has previously been described in colon cancer cells (46).”
BackgroundARID1A loss-of-function induces CpG island methylator phenotype
Yamada, H., Takeshima, H., Fujiki, R., Yamashita, S., Sekine, S., Ando, T., Hattori, N., Okabe, A., Yoshikawa, T., Obama, K., et al. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215587 · Cited by 26
Siddaway, R., Canty, L., Pajovic, S., Milos, S., Coyaud, É., Sbergio, S.-G., Vadivel, A. K. A., Lubanszky, E., Yun, H. Y., Portante, A., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02489-2 · Cited by 27
“However, EZH2 plays a role in DNMT recruitment [75, 81], and it is possible that altered H3K27M-mediated alterations in EZH2 function could mediate the global DNA hypomethylation.”
BackgroundBai, W., Zhang, Y., Ma, J., Du, M., Xu, H., Wang, J., Zhang, L., Li, W., Hou, Y., Liu, X., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04680-w · Cited by 26
“EZH2 epigenetic regulation increased the H3K27me3 level, a hallmark of gene repression [52], and the binding of EZH2 to chromatin is dependent on YY1 [28, 53].”
BackgroundCharacterizing crosstalk in epigenetic signaling to understand disease physiology
Lempiäinen, J. K., & Garcia, B. A. (2023) · Biochemical Journal · doi:10.1042/bcj20220550 · Cited by 29
Dynamic antagonism between key repressive pathways maintains the placental epigenome
Weigert, R., Hetzel, S., Bailly, N., Haggerty, C., Ilik, İ., Yung, P. Y. K., Navarro, C., Bolondi, A., Kumar, A. S., Anania, C., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01114-y · Cited by 27
Liu, E. T. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.07.014 · Cited by 26
“EZH2 is known to be a target of E2F1 and therefore will be activated in cells mutant in the pRB-p16 pathway and is overexpressed in many cancer states, and absent in the normal counterparts [15 ,16].”
BackgroundEpigenetic modifications and self-renewal regulation of mouse germline stem cells
Lee, J., & Shinohara, T. (2011) · Cell Research · doi:10.1038/cr.2011.111 · Cited by 26
Epigenetic and genetic deregulation in cancer target distinct signaling pathway domains
Gao, Y., & Teschendorff, A. E. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1100 · Cited by 25
Charlet, J., Tomari, A., Dallosso, A. R., Szemes, M., Kaselova, M., Curry, T. J., Almutairi, B. O., Etchevers, H., McConville, C. M., Malik, K. T. A., et al. (2016) · Molecular Carcinogenesis · doi:10.1002/mc.22591 · Cited by 27
Finegersh, A., Kulich, S. M., Guo, T. W., Favorov, A. V., Fertig, E. J., Danilova, L., Gaykalova, D. A., Califano, J. A., & Duvvuri, U. (2017) · Scientific Reports · doi:10.1038/s41598-017-15634-9 · Cited by 26
Ginder, G. D., Gnanapragasam, M. N., & Mian, O. Y. (2008) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(07)00004-x · Cited by 26
Genome-wide positioning of bivalent mononucleosomes
Sen, S., Block, K. F., Pasini, A., Baylin, S. B., & Easwaran, H. (2016) · BMC Medical Genomics · doi:10.1186/s12920-016-0221-6 · Cited by 26
The role of DNA methylation in personalized medicine for immune-related diseases
Gupta, M. K., Peng, H., Li, Y., & Xu, C. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108508 · Cited by 25
On epigenetic stochasticity, entropy and cancer risk
Teschendorff, A. E. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2023.0054 · Cited by 24
Gretarsson, K. H., Abini-Agbomson, S., Gloor, S. L., Weinberg, D. N., McCuiston, J. L., Kumary, V. U. S., Hickman, A. R., Sahu, V., Lee, R., Xu, X., et al. (2024) · Science Advances · doi:10.1126/sciadv.adp0975 · Cited by 27
“Analysis of patient tumor samples suggests that CGIs that gain aberrant DNAme are more likely to be enriched for H3K27me3 in human embryonic or adult stem cells ( 11 – 14 ).”
Array-based identification of common DNA methylation alterations in ulcerative colitis
Koizumi, K., Alonso, S., Miyaki, Y., Okada, S., Ogura, H., Shiiya, N., Konishi, F., Taya, T., Perucho, M., & Suzuki, K. (2011) · International Journal of Oncology · doi:10.3892/ijo.2011.1283 · Cited by 26
“It has been found that PRC-target genes, including the Hox gene clusters, are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets (47) and that methylation on Lys27 of histone H3, a modification mediated by the Polycomb repressor complex 2 (PRC2), pre-marks genes for de nov…”
BackgroundReducing DNA methylation suppresses colon carcinogenesis by inducing tumor cell differentiation
Hatano, Y., Semi, K., Hashimoto, K., Lee, M. S., Hirata, A., Tomita, H., Kuno, T., Takamatsu, M., Aoki, K., Taketo, M. M., et al. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv060 · Cited by 25
Loss of H3K27 methylation identifies poor outcomes in adult-onset acute leukemia
van Dijk, A. D., Hoff, F. W., Qiu, Y., Chandra, J., Jabbour, E. J., de Bont, E. S. J. M., Horton, T. M., & Kornblau, S. M. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01011-x · Cited by 25
Heery, R., & Schaefer, M. H. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1167 · Cited by 25
Ryland, K. E., Hawkins, A. G., Weisenberger, D. J., Punj, V., Borinstein, S. C., Laird, P. W., Martens, J. R., & Lawlor, E. R. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0343 · Cited by 25
Samuelsson, J., Dumbović, G., Rivera, C. P., Moreta-Moraleda, C., Alibés, A., Ruiz‐Larroya, T., Gimenez‐Bonafé, P., Alonso, S., Forcales, S. V., & Perucho, M. (2016) · Epigenomes · doi:10.3390/epigenomes1010002 · Cited by 25
“For instance, polycomb directs de novo DNA methylation in cancer cells with enhancer of zeste homolog 2 (EZH2) serving as a recruitment platform for DNA methyltransferases as a possible mechanism [43,47,48].”
BackgroundStelling, A., Wu, C. T., Bertram, K., Hashwah, H., Theocharides, A. P. A., Manz, M. G., Tzankov, A., & Mueller, A. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019000210 · Cited by 25
“To be able to investigate the effects of DAC in an orthotopic model, we took advantage of MISTRG and MISTRG6 mice, which differ from the parental MISTRG strain in their additional expression of human interleukin-6 from a knock-in allele.(14) Although MISTRG mice efficiently supported the orthotopic engraftment of SU-D…”
BackgroundEpigenetic Changes in Cancer as Potential Targets for Prophylaxis and Maintenance Therapy
Grønbæk, K., Treppendahl, M. B., Asmar, F., & Guldberg, P. (2008) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2008.00325.x · Cited by 25
Herberg, M., Siebert, S., Quaas, M., Thalheim, T., Rother, K., Hussong, M., Altmüller, J., Kerner, C., Galle, J., Schweiger, M. R., et al. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0639-8 · Cited by 25
“Here, the recruitment of H3K4me3 in Set2 genes might represent a mechanism to protect their promoters from DNA methylation and thus to ensure potential gene activation according to the following mechanism: DNA damage triggers promoter DNA methylation of H3K27me3 target genes [48].”
BackgroundMundy-Bosse, B. L., Weigel, C., Wu, Y.-Z., Abdelbaky, S., Youssef, Y., Casas, S. B., Polley, N., Ernst, G., Young, K. A., McConnell, K. K., et al. (2022) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-21-0098 · Cited by 24
Epigenetics of Neurological Cancers
Fouse, S. D., & Costello, J. (2009) · Future Oncology · doi:10.2217/fon.09.132 · Cited by 25
Keeping an open mind: highlights and controversies of the breast cancer stem cell theory
Allegrucci, C., & Shah, M. (2012) · Breast Cancer Targets and Therapy · doi:10.2147/bctt.s26434 · Cited by 24
“61 Reprogramming experiments have demonstrated that epigenetic landscapes are plastic and that they can be influenced and manipulated to change cell fate.”
Ward, E., Varešlija, D., Charmsaz, S., Fagan, A., Browne, A. L., Cosgrove, N. S., Cocchiglia, S., Purcell, S. P., Hudson, L., Das, S., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2615 · Cited by 25
The substantial loss of H3K27me3 can stratify risk in grade 2, but not in grade 3 meningioma
Jung, M., Kim, S., Lim, K. Y., Bae, J., Park, C., Choi, S. H., Park, S., & Won, J. (2021) · Human Pathology · doi:10.1016/j.humpath.2021.06.005 · Cited by 24
Histone Methylation and the Initiation of Cancer
Huang, S. (2008) · CRC Press eBooks · doi:10.1201/9781420045802.ch8 · Cited by 25
Xue, Y., Liu, L., Zhang, Y., He, Y., Wang, J., Ma, Z.-C., Li, T.-J., Zhang, J.-Y., Huang, Y.-Y., & Gao, Y.-Q. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02100-0 · Cited by 23
“It was well known that H3K27me3-rich regions, which are often CpG-rich, tend to undergo hypermethylation in carcinogenesis [10, 36].”
BackgroundAberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer
Sugimachi, K., Matsumura, T., Shimamura, T., Hirata, H., Uchi, R., Ueda, M., Sakimura, S., Iguchi, T., Eguchi, H., Masuda, T., et al. (2016) · Annals of Surgical Oncology · doi:10.1245/s10434-016-5289-x · Cited by 23
“Several recent reports have suggested that aberrant DNA methylation in cancer is linked to the bivalent state of promoters.(14,15) In this study, we hypothesized that transcription factors with bivalent CpG-rich promoters in both ES cells and normal colonic mucosal samples could be key regulators of differentiation in…”
BackgroundLiu, T., Zhao, X., Lin, Y., Luo, Q., Zhang, S., Xi, Y., Chen, Y., Lin, L., Fan, W., Yang, J., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0668 · Cited by 24
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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