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Linking DNA methylation and histone modification: patterns and paradigms
Abstract
Both DNA methylation and histone modification are involved in establishing patterns of gene repression during development. Certain forms of histone methylation cause local formation of heterochromatin, which is readily reversible, whereas DNA methylation leads to stable long-term repression. It has recently become apparent that DNA methylation and histone modification pathways can be dependent on one another, and that this crosstalk can be mediated by biochemical interactions between SET domain histone methyltransferases and DNA methyltransferases. Relationships between DNA methylation and histone modification have implications for understanding normal development as well as somatic cell reprogramming and tumorigenesis.
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“On the other hand, the increase in scale presents computational opportunities. It allows benefitting from ‘big data’ approaches, most notably deep learning193, developed in fields such as image and text analysis, in which data sets tend to have many more samples than were available in genomics thus far.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [193]
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“The effect of these modifications is a change in chromatin structure, influencing the activity of the transcriptional machinery at the respective locus (Cedar and Bergman, 2009; Rose and Klose, 2014).”
BackgroundHistone tails regulate DNA methylation by allosterically activating de novo methyltransferase
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MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes
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“In contrast, DNA methylation has an antagonistic relationship with H3K4methylation in regulating gene expression (Cedar and Bergman, 2009).”
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“Firstly, the additional methyl groups prevent certain TFs from recognizing and binding to the DNA (Cedar and Bergman 2009).”
BackgroundEpigenetic Regulations in Neuropsychiatric Disorders
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“These crosstalk events are thought to establish and maintain the local chromatin environment as well as help cells “remember” their differentiated state (Cedar and Bergman, 2009; Jobe et al., 2012).”
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“…FORTH, Heraklion, 70013 Crete, Greece 2 Department of Biology, University of Crete, Heraklion, 71409 Crete, Greece Correspondence should be addressed to Androniki Kretsovali, kretsova@imbb.forth.gr Received 12 October 2011; Accepted 19 December 2011 Academic Editor: Andras…”
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Stress and the epigenetic landscape: a link to the pathobiology of human diseases?
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“Many of these cancer genes, including classic tumour suppressors that have abnormal DNA methylation at their promoters in several types of cancer, are marked by repressive polycomb group (PcG) protein complexes during embryonic developmen”
BackgroundYang, S.-M., Kim, B. J., Toro, L. N., & Skoultchi, A. I. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213266110 · Cited by 127
“U ni ts (x 10 -3 ) WT TKO H1d(1-159) R-5 H1d(1-159) R-26 A H19 Gtl2 Rian Mirg”
BackgroundInfluentialCell cycle progression in response to oxygen levels
Ortmann, B. M., Druker, J., & Rocha, S. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1645-9 · Cited by 131
“Histone tail modification can lead to changes in chromatin structure, which have functional consequences for the several processes occurring in the nucleus [124, 128].”
BackgroundMelas, P. A., Scherma, M., Fratta, W., Cifani, C., & Fadda, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041863 · Cited by 127
“There is accumulating evidence suggesting that DNA methylation works in concert with histone modifications to regulate gene expression [41].”
BackgroundDevelopment of Fluorogenic Probes for Quick No-Wash Live-Cell Imaging of Intracellular Proteins
Hori, Y., Norinobu, T., Sato, M., Arita, K., Shirakawa, M., & Kikuchi, K. (2013) · Journal of the American Chemical Society · doi:10.1021/ja405745v · Cited by 123
Role of Chromatin Architecture in Plant Stress Responses: An Update
Bhadouriya, S. L., Mehrotra, S., Basantani, M. K., Loake, G. J., & Mehrotra, R. (2021) · Frontiers in Plant Science · doi:10.3389/fpls.2020.603380 · Cited by 123
Whole-genome analysis of the methylome and hydroxymethylome in normal and malignant lung and liverPreprint
Li, X., Liu, Y., Salz, T., Hansen, K. D., & Feinberg, A. P. (2016) · Genome Research · doi:10.1101/gr.211854.116 · Cited by 119
“Given histone modifications were usually coupledwiththestatusofgeneexpressionandwerenotasstableas 5mC (Cedar and Bergman 2009), the strong associations between 5hmCandactivehistonemodifications suggestthat5hmCmaybe a mark for active genes and can be more dynamically regulated by cells compared to…”
Coordinate Regulation of DNA Methylation and H3K27me3 in Mouse Embryonic Stem Cells
Hagarman, J. A., Motley, M. P., Kristjánsdóttir, K., & Soloway, P. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053880 · Cited by 126
Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis
Tang, Y.-N., Ding, W., Guo, X.-J., Yuan, X., Wang, D., & Song, J. (2015) · Nature Communications · doi:10.1038/ncomms9230 · Cited by 122
Dual recognition of H3K4me3 and H3K27me3 by a plant histone reader SHL
Qian, S., Lv, X., Scheid, R. N., Lü, L., Yang, Z., Chen, W., Liu, R., Boersma, M., Denu, J. M., Zhong, X., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04836-y · Cited by 126
“d The binding between PtSHL and H3(1-35) K4me3K27me3 peptide yielded a binding affinity nearly identical as PtSHL-H3K4me3 and PtSHL-H3K27me3 and with an N-value of 1.”
BackgroundGenome‐wide DNA methylation profiles in precancerous conditions and cancers
Kanai, Y. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01383.x · Cited by 120
Epigenetic modifications of the immune system in health and disease
Obata, Y., Furusawa, Y., & Hase, K. (2015) · Immunology and Cell Biology · doi:10.1038/icb.2014.114 · Cited by 125
The Role of Heavy Metal Pollution in Neurobehavioral Disorders: a Focus on Autism
Gorini, F., Muratori, F., & Morales, M. A. (2014) · Review Journal of Autism and Developmental Disorders · doi:10.1007/s40489-014-0028-3 · Cited by 120
“Epigenetic mechanisms (e.g., DNA methylation, histone modifications, and expression of non-coding microRNAs) produce heritable modifications in gene expression without changes in DNA sequence (Chuang and Jones 2007; Cedar and Bergman 2009; Svoboda and Flemr 2010).”
BackgroundEpigenetics of hepatocellular carcinoma
Toh, T. B., Lim, J. J., & Chow, E. K. (2019) · Clinical and Translational Medicine · doi:10.1186/s40169-019-0230-0 · Cited by 125
DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse
Zhou, W., Hinoue, T., Barnes, B., Mitchell, O. D., Iqbal, W., Lee, S. M., Foy, K. K., Lee, K., Moyer, E. J., VanderArk, A., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100144 · Cited by 116
“Mouse models have profoundly impacted basic and translational biological research, contributing to many important discoveries in the past century, including the elucidation of basic principles of epigenetics (Adalsteinsson and Ferguson-Smith, 2014; Anderson et al., 2012; Bartolomei et al., 1991; Bird, 2002; Cedar and…”
BackgroundKlughammer, J., Romanovskaia, D., Nemc, A., Posautz, A., Seid, C. A., Schuster, L. C., Keinath, M. C., Ramos, J. S. L., Kosack, L., Evankow, A. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-34828-y · Cited by 131
Helper T-cell differentiation and plasticity: insights from epigenetics
Hirahara, K., Vahedi, G., Ghoreschi, K., Yang, X., Nakayamada, S., Kanno, Y., O’Shea, J. J., & Laurence, A. D. J. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03483.x · Cited by 119
The rejuvenated scenario of epithelial–mesenchymal transition (EMT) and cancer metastasis
Meng, F., & Wu, G. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9379-3 · Cited by 123
“Histone acetylation is another epigenetic change that regulates gene expression by modulating chromatin structure [90, 91].”
BackgroundLi, W., Han, Y., Tao, F., & Chong, K. (2011) · Journal of Plant Physiology · doi:10.1016/j.jplph.2011.05.020 · Cited by 122
“Recent studies have suggested that de novo methylation in the mbryo may be excluded at CG islands because of the presence of 3K4me (Cedar and Bergman, 2009).”
BackgroundJiang, Y., Jakovcevski, M., Bharadwaj, R., Connor, C., Schroeder, F. A., Lin, C. L., Straubhaar, J., Martin, G., & Akbarian, S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1314-10.2010 · Cited by 118
“Of note, various chromatin remodeling complexes associated with transcriptional repression involve histone methyltransferases (HMTs) for histone H3-lysine 9 (H3K9) and other lysine residues (Cedar and Bergman, 2009).”
BackgroundLi, R., Ong, S. L., Tran, L. M., Jing, Z., Liu, B., Park, S. J., Huang, Z. L., Walser, T. C., Heinrich, E. L., Lee, G., et al. (2020) · Scientific Reports · doi:10.1038/s41598-019-57285-y · Cited by 124
Kanwal, R., & Gupta, S. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00066.2010 · Cited by 124
Epigenetic mechanisms of drug addiction
Feng, J., & Nestler, E. J. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.001 · Cited by 113
“For example, certain histone methylation events are preferentially enriched at methylated DNA sites [49].”
Lau, S.-F., Chen, C., Fu, W.-Y., Qu, J. Y., Cheung, T. H., Fu, A. K. Y., & Ip, N. Y. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107530 · Cited by 114
“To examine how the chromatin-accessible regions of DEGs regulate gene expression, we used chromatin immunoprecipitation sequencing (ChIP-seq) to examine the genome-wide H3K4me3 landscape, which marks active promoter regions (Cedar and Bergman, 2009), in the microglia in IL-33-injected APP/PS1 mice.”
MethodChromatin Regulator PRC2 Is a Key Regulator of Epigenetic Plasticity in Glioblastoma
Natsume, A., Ito, M., Katsushima, K., Ohka, F., Hatanaka, A., Shinjo, K., Sato, S., Takahashi, S., Ishikawa, Y., Takeuchi, I., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0109 · Cited by 123
“is highly stable without artificially altering key factors in the cells (16).”
BackgroundKaaij, L. J. T., van de Wetering, M., Fang, F., Decato, B. E., Molaro, A., van de Werken, H. J. G., van Es, J. H., Schuijers, J., de Wit, E., de Laat, W. L., et al. (2013) · Genome biology · doi:10.1186/gb-2013-14-5-r50 · Cited by 118
“Indeed, TSS methylation is well-known to accompany the long term silencing of gene expression [19,20], suggesting that the observations we describe here reflect the long-term separation of the lineages leading to intestinal and epidermal cell fates.”
BackgroundEpigenetics and developmental programming of welfare and production traits in farm animals
Sinclair, K. D., Rutherford, K., Wallace, J. M., Brameld, J. M., Stöger, R. J., Alberio, R., Sweetman, D., Gardner, D. S., Perry, V. E. A., Adam, C. L., et al. (2016) · Reproduction Fertility and Development · doi:10.1071/rd16102 · Cited by 124
“These processes are best understood in the mouse (Cedar and Bergman 2009; Tomizawa et al. 2012), with only limited data available in ruminants (Thurston et al.”
BackgroundKing, A., Huang, K. Y., Rubbi, L., Liu, S., Wang, C., Wang, Y., Pellegrini, M. A., & Fan, G. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.083 · Cited by 123
Metadata
- Authors
- Cedar, H., & Bergman, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Cedar, Howard
- Venue
- Nature Reviews Genetics
- Published
- 2009-05
- Volume
- 10
- Issue
- 5
- Pages
- 295-304
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W1976626368
- Cited by
- 2,267
- References
- 108
- Citations by year
- 2026: 50 · 2025: 68 · 2024: 87 · 2023: 90 · 2022: 107 · 2021: 135 · 2020: 130 · 2019: 119 · 2018: 131 · 2017: 165 · 2016: 169 · 2015: 183 · 2014: 169 · 2013: 163 · 2012: 184
- FWCI
- 12.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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
- DNA methylation, histone modifications, epigenetic crosstalk, gene repression, heterochromatin, DNA methyltransferases, chromatin structure, somatic cell reprogramming, carcinogenesis, development (biology)
- MeSH terms
- Histone Methyltransferases, Animals, DNA, Heterochromatin, Histones, Humans, Models, Biological, Neoplasms, Histone-Lysine N-Methyltransferase, DNA-Cytosine Methylases, DNA Methylation
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