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Mol Cell. 2018 Sep 6;71(5):848-857.e6. doi: 10.1016/j.molcel.2018.07.005. Epub 2018 Aug 2.

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

Author information

1
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: bing.yao@emory.edu.
2
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
3
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Biostatistics and Bioinformatics, Emory University School of Medicine, Atlanta, GA 30322, USA.
4
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
5
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
6
Department of Biostatistics and Bioinformatics, Emory University School of Medicine, Atlanta, GA 30322, USA.
7
State Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, Hunan 410078, China.
8
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: peng.jin@emory.edu.

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.

KEYWORDS:

6-methyladenine; Polycomb; epigenetics; neuron

PMID:
30078725
PMCID:
PMC6136845
DOI:
10.1016/j.molcel.2018.07.005
[Indexed for MEDLINE]
Free PMC Article

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