N6-Methyladenine DNA Modification in the Human Genome
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Abstract
DNA N 6-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in the human genome, and we cataloged 881,240 6mA sites accounting for ∼0.051% of the total adenines. [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification. 6mA sites were enriched in the coding regions and mark actively transcribed genes in human cells. DNA 6mA and N 6-demethyladenine modification in the human genome were mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The abundance of 6mA was significantly lower in cancers, accompanied by decreased N6AMT1 and increased ALKBH1 levels, and downregulation of 6mA modification levels promoted tumorigenesis. Collectively, our results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis.
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Reported differences in 6mA distribution between mouse and human may represent tissue-specific patterns rather than species differences, because the tissues used were unique to each species.
“Reported difference in 6mA distribution between mouse and human may represent tissue specific patterns rather than species differences, since the tissues used for the mouse and human studies were unique to each species (mESC and blood DNA, respectively (60, 61)).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [60]
These findings are supported by the identification of both a methyltransferase and a demethylase for deposition and removal of 6mA.
“These findings are supported by the identification of both methyltransferase and demethylase for deposition and removal of 6mA, respectively (60, 61).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [60]
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- Authors
- Xiao, C.-L., Zhu, S., He, M., Chen, D., Zhang, Q., Chen, Y., Yu, G., Liu, J., Xie, S.-Q., Luo, F., Liang, Z., Wang, D.-P., Bo, X.-C., Gu, X.-F., Wang, K., & Yan, G.-R.
- Affiliations
- Sun Yat-sen University (CN)
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Chinese Academy of Agricultural Sciences (CN)
- Grandomics (China) (CN)
- Guangzhou Medical University (CN)
- Clemson University (US)
- National University of Singapore (SG)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Wang, Kai
- Yan, Guang-Rong
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 71
- Issue
- 2
- Pages
- 306-318.e7
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2949348780
- Cited by
- 531
- References
- 49
- Citations by year
- 2026: 23 · 2025: 61 · 2024: 57 · 2023: 69 · 2022: 72 · 2021: 84 · 2020: 82 · 2019: 61 · 2018: 18 · 2016: 1
- FWCI
- 21.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81772998, 81672393)
- R&D Plan of Guangzhou and Guangdong (201704020115, 2017A020215096)
- Yangcheng Scholars program from the Ministry of Education of Guangzhou (1201561583)
- Innovative Research Team of Ministry of Education of Guangzhou (1201610015)
- National Funds of Developing Local Colleges and Universities (B16056001)
- Fundamental Research Funds for the Central Universities (15ykjc23d)
- Guangdong Natural Science Foundation (2015A030313127)
- China Postdoctoral Science Foundation (2017M612798)
- NIH (HG006465)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- N6-methyladenosine, DNA methylation, ALKBH1, demethylases, methyltransferase, carcinogenesis, cancer, human genome, DNA modification
- MeSH terms
- AlkB Homolog 1, Histone H2a Dioxygenase, Adenine, Animals, DNA, Humans, Mice, Nude, Site-Specific DNA-Methyltransferase (Adenine-Specific), Genome, Human, DNA Methylation, Mice, Carcinogenesis, Heterografts
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