Cited by 1,199Epigenetics and DNA MethylationGenomics and Chromatin DynamicsCancer-related gene regulation

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Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer

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Yang, Xiaojing, Han, Han, De Carvalho, Daniel D., Lay, Fides D., Jones, Peter A., Liang, Gangning·2014·Cancer Cell

DOI 10.1016/j.ccr.2014.07.028PMC PMC4224113

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Abstract

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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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
ORCID: Yang, Xiaojing
Han, Han
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)
DOI: 10.1016/j.ccr.2014.07.028
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
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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Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer

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