Cited by 2,267Epigenetics and DNA MethylationGenomics and Chromatin DynamicsCancer-related gene regulation

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Linking DNA methylation and histone modification: patterns and paradigms

Cedar, Howard, Bergman, Yehudit·2009·Nature Reviews Genetics

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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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Background
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Background
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BackgroundInfluential
Integrative functional genomic analysis identifies epigenetically regulated fibromodulin as an essential gene for glioma cell migration
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“Other than conducting their mutually exclusive purposes, histone modifications and DNA methylation interact at numerous levels to modulate gene expression changes and chromatin organization (33).”
Background
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Loughland, I., Little, A. G., & Seebacher, F. (2021) · BMC Biology · doi:10.1186/s12915-020-00942-w · Cited by 56
“Furthermore, DNA methylation and histone modifications (acetylation and methylation) can interact to determine phenotypic responses [19].”
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Epigenetic regulation of gene expression in response to environmental exposures: From bench to model
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“In response to physiological and developmental signals, histones create variations in packaging and accessibility of DNA (Cedar and Bergman, 2009).”
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Bhunjun, C. S., Chen, Y. J., Phukhamsakda, C., Boekhout, T., Groenewald, J. Z., McKenzi, E. H. C., Francisco, E. C., Frisvad, J. C., Groenewald, M., Hurdeal, V. G., et al. (2024) · Studies in Mycology · doi:10.3114/sim.2024.108.01 · Cited by 58
DNA methylation of genes in adipose tissue
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“DNA methylation is thought to be intricately related to histone modification((51)) and a strong negative correlation exists between DNA methylation and trimethylation of histone H3 at Lys.”
Background
Restoring Fertility in Sterile Childhood Cancer Survivors by Autotransplanting Spermatogonial Stem Cells: Are We There Yet?
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“With respect to overall epigenetic control of cellular genes, cross talk between histone modifications and DNA methylation is well recognized, but highly complex and poorly understood (63).”
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Combined Large-Scale Phenotyping and Transcriptomics in Maize Reveals a Robust Growth Regulatory Network
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“…are intertwined with DNA methylation, for instance by interaction between chromatin modifiers such as SET domain proteins and DNA methyltransferases (Cedar and Bergman, 2009) and/or methylCpG-binding domain proteins (MBDs; Zemach and Grafi, 2007), which read out the DNA methylation pattern.”
Background
Impaired Regulation of Histone Methylation and Acetylation Underlies Specific Neurodevelopmental Disorders
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“Histone modifications are one example of epigenetic alteration, and represent a key mechanism through which local gene expression is regulated (Cedar and Bergman, 2009).”
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“…markers (MTHFR rs1801131 C, MTR rs1805087 G and MTRR rs1801394 G alleles) DNA methylation is a major epigenetic modification that suppresses gene expression by modulating the access of the transcription machinery to the chromatin or by recruiting methyl binding proteins (Cedar and Bergman, 2009).”
Background
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“Promoter methylation and the histone modifications H3K9me3 or H3K27me3 are known repressive chromatin marks (48).”
Background
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“Changes in DNA methylation have been shown to modulate histone methylation, which may act cooperatively to influence chromatin structure and thereby regulate gene expression 24 .”
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“112 113 – 115 DNA methylation and non-coding RNAs DNA methylation can regulate the expression of non-coding RNAs including miRNAs.”
Background
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“Although both DNA methylation and histone modifications are involved in affecting chromatin conformation, DNA methylation presumably elicits a long-term effect by stabilizing the repression of these genomic regions, while histone modifications involve only short-term, temporary changes in local chromatin structure [23…”
Background
The impact of histone post-translational modifications in neurodegenerative diseases
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“[67] Traditionally, it was thought that these modifications’ only role was to modulate the strength of the physical interactions between DNA and the histone octamer leading to alterations in gene transcription.[68] For instance, acetylation decreases the positive charge on histones and lessens the strength of the inte…”
Background
Identification of DNA motifs that regulate DNA methylation
Wang, M., Zhang, K., Ngo, V., Liu, C., Fan, S., Whitaker, J. W., Chen, Y., Ai, R., Chen, Z., Wang, J., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz483 · Cited by 57
“Both DNA methylation and histone modification play important roles in regulating gene expression and their interplay has been well recognized (87,88).”
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“In particular, 192 the epigenetic mechanism of DNA methylation is a prime candidate; developmental 193 establishment of DNA methylation is affected by the environment (90) and, once established, is 194 maintained with high fidelity (30), enabling the long-lasting stability that is the hallmark of 195 developmental pro…”
Background
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“The Polycomb target genes provide the first example of how histone modification and DNA methylation work together to achieve silencing, and the mechanism of transcriptional repression in such a case involves the generation of local heterochromatin- the histone methyltransferase EZH2, H3K27me3 and the methylated DNA ‘l…”
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“However, evidence shows now that there is a large redundancy present in the functions of the different DNMTs [19,20].”
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Temperature influences histone methylation and mRNA expression of the Jmj-C histone-demethylase orthologues during the early development of the oyster Crassostrea gigas
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“This might be related to the fact that the majority of those CpG sites had measurable levels of methylation in C2 ( 1%) and were thus already repressed, consistent with previous reports (27).”
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“Another connection between HMTs and DNA methylation is that some SET-domain containing HMTs physically recruit DNA methyltransferase leading to CpG methylation (42).”
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“…protrude out of the nucleosome and these are the areas that are typically accessible for the chemical modifications, such as acetylation, methylation, phosphorylation, ubiquitination, sumoylation, ADP-ribosylation, and others (Cedar & Bergman, 2009; Rose & Klose, 2014; Rothbart & Strahl, 2014).”
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“There is also evidence that some heterochromatic histone modifications crosstalk with and may derive their stability from DNA methylation [105, 106].”
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“While histone PTMs are considered to primarily promote reversible repression of specific genes, DNA methylation contributes to long-lasting effects [115].”
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“Interestingly, several methylation features ( TSS1500_avgMval, first_exon_avgMval and UTR5_avgMval ) are clustered with histone modification features, suggesting collinearity between these two types of features, as shown by others [28,29].”
Background
Histone modifications as a pathogenic mechanism of colorectal tumorigenesis
Gargalionis, A. N., Piperi, C., Adamopoulos, C., & Papavassiliou, A. G. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.05.002 · Cited by 53
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“A mutually reinforcing cross-talk between histone modifications and DNA methylation is involved in cell cycle progression in both plants and mammals [47,48].”
5-hydroxymethylcytosine
Ye, C., & Li, L. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.27144 · Cited by 56
Distinct nuclear localization patterns of DNA methyltransferases in developing and mature mammalian retina
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The Genetic and Epigenetic Journey of Embryonic Stem Cells into Mature Neural Cells
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“There are pivotal crosstalks between 5mC and histone PTM (Fuks, 2005; Cedar and Bergman, 2009), which for example, are evident in heterochromatin with high levels of H3K9me3 equating with 5mC (Stancheva, 2005).”
BackgroundInfluential
Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells
Tykocinski, L., Sinemus, A., Rezavandy, E., Weiland, Y., Baddeley, D., Cremer, C. G., Sonntag, S., Willecke, K., Derbinski, J., & Kyewski, B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009265107 · Cited by 53
“Both epigenetic modifications can influence each other and the relationship can work in both directions (14).”
Background

Authors: Cedar, H., & Bergman, Y.
Affiliations: Hebrew University of Jerusalem (IL)
Corresponding author: Cedar, Howard
ORCID: Cedar, Howard
Bergman, Yehudit
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2009-05
Volume: 10
Issue: 5
Pages: 295-304
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/nrg2540
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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Linking DNA methylation and histone modification: patterns and paradigms

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