Details

Autor(en) / Beteiligte

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

Titel

N6-Methyladenine DNA Modification in the Human Genome

Ist Teil von

• Molecular cell, 2018-07, Vol.71 (2), p.306-318.e7

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •DNA 6mA modification is extensively present in the human genome•Methyltransferase N6AMT1 is responsible for DNA 6mA methylation modification•Demethylase ALKBH1 is responsible for DNA 6mA demethylation modification•Decrease of genomic DNA 6mA promotes human tumorigenesis Xiao et al. show that DNA methylation on N6-adenine exists in the human genome. The mark is added by the methyltransferase N6AMT1 and it is removed by the demethylase ALKBH1. Decrease of genomic DNA 6mA promotes tumorigenesis and is associated with poor prognosis for cancer patients.