N6-methyladenine DNA modification in the human genome.

Authors: Xiao, Chuan-Le and Zhu, Song and He, Minghui and Chen, De and Zhang, Qian and Chen, Ying and Yu, Guoliang and Liu, Jinbao and Xie, Shang-Qian and Luo, Feng and Liang, Zhe and Wang, De-Peng and Bo, Xiao-Chen and Gu, Xiao-Feng and Wang, Kai and Yan, Guang-Rong

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. Copyright © 2018 Elsevier Inc. All rights reserved.

Journal: Molecular cell
DOI: 10.1016/j.molcel.2018.06.015
Year: 2018

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