The decreased N6-methyladenine DNA modification in cancer cells.
N6-methyladenine (6 mA) is a recently characterized DNA modification in mammalian genomes, although its biological importance remains to be resolved. Using a highly sensitive HPLC/MS/MS approach, here we report regulation of 6 mA modification in mammalian cells. To these aspects, down-regulation of 6 mA modification was first characterized in human cancer cells and tissues, relative to their normal controls. In contrast to the relative stable 5 mC modification, a dramatic decrease of 6 mA modification was found, showing that 6 mA is the most regulated DNA modification in cancers. In addition to the regulation in cancer cells, a hundreds-fold increase of 6 mA modification was found for in vitro cultured human cells, relative to the in vivo cells. This up-regulation was also confirmed with in vitro cultured mouse cells. Taken together, our study revealed distinct 6 mA modification profiles in the cancer and cultured cells. Considering its distinct regulation from that of 5 mC, our study suggests that 6 mA DNA modification may play a crucial role in cell fate transition of mammalian cells.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Da
D
Liang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Hong
H
Wang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Wei
W
Song
Department of Pharmacy, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Xin
X
Xiong
Department of Pharmacy, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Xianhua
X
Zhang
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
Zhiping
Z
Hu
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
Huahu
H
Guo
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Zhenjun
Z
Yang
Department of Pharmacy, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Suodi
S
Zhai
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Li-He
LH
Zhang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China. Electronic address: yemin@bjmu.edu.cn.
Min
M
Ye
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing, 100191, China. Electronic address: quan.du@pku.edu.cn.
Quan
Q
Du
D041721:3T3-L1 Cells; D044503:5-Methylcytosine / Q000032:analysis / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004247:DNA / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics*; D053719:Tandem Mass Spectrometry / Q000379:methods
D044503:5-Methylcytosine; D000225:Adenine; D004247:DNA; C000730567:6-methyladenine
Cancer; DNA modification; Epigenetic