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N6-Methyladenine DNA Modification in Drosophila

2015; Cell Press; Volume: 161; Issue: 4 Linguagem: Inglês

10.1016/j.cell.2015.04.018

1097-4172

Guoqiang Zhang, Hua Huang, Di Liu, Ying Cheng, Xiaoling Liu, Wenxin Zhang, Ruichuan Yin, Dapeng Zhang, Peng Zhang, Jianzhao Liu, Chaoyi Li, Baodong Liu, Yuewan Luo, Yuanxiang Zhu, Ning Zhang, Shunmin He, Chuan He, Hailin Wang, Dahua Chen,

Advanced biosensing and bioanalysis techniques

DNA N6-methyladenine (6mA) modification is commonly found in microbial genomes and plays important functions in regulating numerous biological processes in bacteria. However, whether 6mA occurs and what its potential roles are in higher-eukaryote cells remain unknown. Here, we show that 6mA is present in Drosophila genome and that the 6mA modification is dynamic and is regulated by the Drosophila Tet homolog, DNA 6mA demethylase (DMAD), during embryogenesis. Importantly, our biochemical assays demonstrate that DMAD directly catalyzes 6mA demethylation in vitro. Further genetic and sequencing analyses reveal that DMAD is essential for development and that DMAD removes 6mA primarily from transposon regions, which correlates with transposon suppression in Drosophila ovary. Collectively, we uncover a DNA modification in Drosophila and describe a potential role of the DMAD-6mA regulatory axis in controlling development in higher eukaryotes.