The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer
Open accessAbstract
DNA methylation in promoters is well known to silence genes and is the presumed therapeutic target of methylation inhibitors. Gene body methylation is positively correlated with expression, yet its function is unknown. We show that 5-aza-2'-deoxycytidine treatment not only reactivates genes but decreases the overexpression of genes, many of which are involved in metabolic processes regulated by c-MYC. Downregulation is caused by DNA demethylation of the gene bodies and restoration of high levels of expression requires remethylation by DNMT3B. Gene body methylation may, therefore, be an unexpected therapeutic target for DNA methylation inhibitors, resulting in the normalization of gene overexpression induced during carcinogenesis. Our results provide direct evidence for a causal relationship between gene body methylation and transcription.
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“Increased CGI gene body methylation positively correlates with transcriptional activation [6, 25, 55]”
From Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression (2024) · cites this paper as [55]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“It is well-known that promoter CGI hypermethylation represses transcription [43, 45], whereas hypermethylation at gene body CGIs activates gene expression [6, 55].”
From Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression (2024) · cites this paper as [55]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“and that the location of these CGIs determines the direction of this regulation [6, 43, 45, 55]”
From Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression (2024) · cites this paper as [55]
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“Another study demonstrated a positive correlation between gene expression and gene body methylation.55”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [55]
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“it is widely accepted that the level of methylation in the regions known as CGI regulates gene expression”
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Cites
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Self-citationConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking
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The diverse roles of DNA methylation in mammalian development and disease
Greenberg, M., & Bourc’his, D. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0159-6 · Cited by 2,272
Function and information content of DNA methylation
Schübeler, D. (2015) · Nature · doi:10.1038/nature14192 · Cited by 2,060
Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.056 · Cited by 1,527
Self-citationTargeting the cancer epigenome for therapy
Jones, P. A., Issa, J. J., & Baylin, S. B. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.93 · Cited by 1,153
Self-citationEpigenetics of colorectal cancer: biomarker and therapeutic potential
Jung, G., Hernández-Illán, E., Moreira, L., Balaguer, F., & Goel, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0230-y · Cited by 813
Metadata
- Authors
- Yang, X., Han, H., De Carvalho, D. D., Lay, F. D., Jones, P. A., & Liang, G.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Jones, Peter A.
- Liang, Gangning
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 26
- Issue
- 4
- Pages
- 577-590
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4224113
- OpenAlex
- W2055986128
- Cited by
- 1,199
- References
- 62
- Citations by year
- 2026: 61 · 2025: 77 · 2024: 104 · 2023: 109 · 2022: 105 · 2021: 120 · 2020: 120 · 2019: 134 · 2018: 128 · 2017: 97 · 2016: 79 · 2015: 55 · 2014: 8
- FWCI
- 32.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Princess Margaret Cancer Foundation
- National Institutes of Health
- National Cancer Institute (R01CA170550, R01CA124518, R01CA082422, P30CA014089, R37CA082422)
- 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
- gene body methylation, DNA methylation, decitabine, DNA demethylation, DNMT3B, c-Myc, gene overexpression, transcriptional regulation, DNA methylation inhibitors, cancer therapy, carcinogenesis, metabolic genes
- MeSH terms
- Cell Division, Colonic Neoplasms, Humans, Promoter Regions, Genetic, Gene Expression, DNA Methylation
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