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N6-Methyladenine DNA Modification in Human Genome

By Chuan-Le Xiao, Song Zhu, Ming-Hui He, Ying Chen, Guo-Liang Yu, De Chen, Shang-Qian Xie, Feng Luo, Zhe Liang, Xiao-Feng Gu, Kai Wang, Guang-Rong Yan

Posted 16 Aug 2017
bioRxiv DOI: 10.1101/176958 (published DOI: 10.1016/j.molcel.2018.06.015)

In human cells, DNA 5-methylcytosine (5mC) modification plays an important role as an epigenetic mark. However, DNA N6-methyladenine modification (6mA), which is predominantly present in prokaryotes and a limited number of eukaryotes, is considered to be absent in human genomic DNA. Here, we show that 6mA is present in human genome, and we identified 881,240 6mA sites whose density is about 0.051% of the total adenines in the human genome DNA, but more than 0.18% in the mitochondrion genome. [G/C]AGG[C/T] was the most significant motif associated with 6mA modification. 6mA sites are enriched in the exon coding regions (P=0.02) and associated with transcriptional activation (P<0.001). We further identify that DNA N6-methyladenine and N6-demethyladenine modification is mediated by 6mA methytransferase N6AMT1 and 6mA demethytransferase ALKBH1, respectively. The 6mA abundance is significantly lower in cancer tissues compared to adjacent normal tissues, always accompanying with lower N6AMT1 and higher ALKBH1 level. Collectively, we uncover a DNA modification in human and describe a potential role of the N6AMT1/ALKBH1-6mA regulatory axis in the progression of human disease, such as cancer.

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