The interplay between DNA and histone methylation: molecular mechanisms and disease implications
Open accessAbstract
Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. A strong correlation exists between the genome-wide distribution of DNA and histone methylation, suggesting an intimate relationship between these epigenetic marks. Indeed, accumulating literature reveals complex mechanisms underlying the molecular crosstalk between DNA and histone methylation. These in vitro and in vivo discoveries are further supported by the finding that genes encoding DNA- and histone-modifying enzymes are often mutated in overlapping human diseases. Here, we summarize recent advances in understanding how DNA and histone methylation cooperate to maintain the cellular epigenomic landscape. We will also discuss the potential implication of these insights for understanding the etiology of, and developing biomarkers and therapies for, human congenital disorders and cancers that are driven by chromatin abnormalities.
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Methylation of H3K9 and H3K27 leads to repressed gene expression, while H3K4 methylation in promoter regions results in relaxed chromatin that promotes gene expression.
“methylation of H3K9 and H3K27 leads to repressed gene expression;163 while histone methylation of H3K4 in the promoter regions results in relaxed chromatin, which promotes gene expression.164”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [163]
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Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“For example, methylation of H3K9 and H3K27 leads to repressed gene expression; 163 while histone methylation of H3K4 in the promoter regions results in relaxed chromatin, which promotes gene expression.”
Background
- Authors
- Li, Y., Chen, X., & Lu, C.
- Affiliations
- Columbia University Irving Medical Center (US)
- Venue
- The EMBO Reports
- Published
- 2021-04-12
- Volume
- 22
- Issue
- 5
- Pages
- e51803-e51803
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC8097341
- OpenAlex
- W3155543161
- Cited by
- 223
- References
- 24
- Citations by year
- 2026: 25 · 2025: 68 · 2024: 51 · 2023: 41 · 2022: 29 · 2021: 9
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of General Medical Sciences (R35GM138181)
- Pew Charitable Trusts
- 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 methylation, CpG, chromatin modification, epigenetic crosstalk, DNA methyltransferases, histone methyltransferase, genome stability, chromatin accessibility, congenital disorders, cancer epigenetics, biomarkers, epigenetic therapy
- MeSH terms
- Chromatin, DNA, Histones, Humans, Methylation, Protein Processing, Post-Translational, DNA Methylation, Epigenesis, Genetic
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