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Active N6-Methyladenine Demethylation by DMAD Regulates Gene Expression by Coordinating with Polycomb Protein in Neurons.

ABSTRACT: A ten-eleven translocation (TET) ortholog exists as a DNA N6-methyladenine (6mA) demethylase (DMAD) in Drosophila. However, the molecular roles of 6mA and DMAD remain unexplored. Through genome-wide 6mA and transcriptome profiling in Drosophila brains and neuronal cells, we found that 6mA may epigenetically regulate a group of genes involved in neurodevelopment and neuronal functions. Mechanistically, DMAD interacts with the Trithorax-related complex protein Wds to maintain active transcription by dynamically demethylating intragenic 6mA. Accumulation of 6mA by depleting DMAD coordinates with Polycomb proteins and contributes to transcriptional repression of these genes. Our findings suggest that active 6mA demethylation by DMAD plays essential roles in fly CNS by orchestrating through added epigenetic mechanisms.

SUBMITTER: Yao B 

PROVIDER: S-EPMC6136845 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Active N<sup>6</sup>-Methyladenine Demethylation by DMAD Regulates Gene Expression by Coordinating with Polycomb Protein in Neurons.

Yao Bing B   Yao Bing B   Li Yujing Y   Wang Zhiqin Z   Chen Li L   Poidevin Mickael M   Zhang Can C   Lin Li L   Wang Feng F   Bao Han H   Jiao Bin B   Lim Junghwa J   Cheng Ying Y   Huang Luoxiu L   Phillips Brittany Lynn BL   Xu Tianlei T   Duan Ranhui R   Moberg Kenneth H KH   Wu Hao H   Jin Peng P  

Molecular cell 20180802 5

A ten-eleven translocation (TET) ortholog exists as a DNA N<sup>6</sup>-methyladenine (6mA) demethylase (DMAD) in Drosophila. However, the molecular roles of 6mA and DMAD remain unexplored. Through genome-wide 6mA and transcriptome profiling in Drosophila brains and neuronal cells, we found that 6mA may epigenetically regulate a group of genes involved in neurodevelopment and neuronal functions. Mechanistically, DMAD interacts with the Trithorax-related complex protein Wds to maintain active tra  ...[more]

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