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N6-Methyladenine DNA Modification in the Human Genome.

Author information

Affiliations

  • 1. Biomedicine Research Center, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; College of Plant Protection, Hunan Agricultural University, Changsha 410128, China.
      Authors
    • Xiao CL 1
    (1 author)
  • 2. Biomedicine Research Center, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
      Authors
    • Zhu S 2
    • Chen 2
    • Yan GR 2
    (3 authors)
  • 3. CookGene Biosciences Center, Guangzhou 510320, China.
      Authors
    • He M 3
    (1 author)
  • 4. Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
      Authors
    • Zhang Q 4
    • Gu XF 4
    (2 authors)
  • 5. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
      Authors
    • Chen Y 5
    • Xie SQ 5
    (2 authors)
    • Show all (11)

ORCIDs linked to this article

Molecular Cell, 12 Jul 2018, 71(2):306-318.e7
https://doi.org/10.1016/j.molcel.2018.06.015 PMID: 30017583 

This article is based on a previously available preprint.

Abstract 

DNA N6-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 N6-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.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.molcel.2018.06.015

Read article for free, from open access legal sources, via Unpaywall: http://www.cell.com/article/S109727651830460X/pdfUnpaywall

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Funding 

Funders who supported this work.

China Postdoctoral Science Foundation (1)

Fundamental Research Funds for the Central Universities (1)

Guangdong Natural Science Foundation (1)

Innovative Research Team of Ministry of Education of Guangzhou (1)

NIH (1)

National Funds of Developing Local Colleges and Universities (1)

National Natural Science Foundation of China (2)

R&D Plan of Guangzhou and Guangdong (2)

Yangcheng Scholars program from the Ministry of Education of Guangzhou (1)