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Author Notes:

Correspondence should be addressed to Bing Yao (bing.yao@emory.edu) or Peng Jin (peng.jin@emory.edu)

B.Y., Y.L., and P.J. conceived and designed the project.

B.Y., Y. L., Z.W., M.P., C.Z., L.L., F.W., H.B., B.J., J.L., Y.C. and L.H. performed the experiments.

B.Y. L.C., T.X. and H.W. performed the bioinformatics analyses.

R.D., and K.M contributed the reagents.

B.P. edited the manuscript.

B.Y. and P.J. wrote the manuscript.

All authors commented on the manuscript.

We would like to thank S. Warren, K. Garber and D. Cook for critical reading of the manuscript.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This work was supported in part by National Institutes of Health (NS051630, NS079625, NS097206, NS091859, MH102690, AG052476 and HG008935 to P.J.), March of Dimes (6-FY13-121 to P.J.), and the Emory Genetics Discovery Fund.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • DNA METHYLATION PATTERNS
  • DROSOPHILA
  • GENOME
  • ELEMENTS
  • N-6-ADENINE
  • MEMORY

Active N-6-Methyladenine Demethylation by DMAD Regulates Gene Expression by Coordinating with Polycomb Protein in Neurons

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Journal Title:

Molecular Cell

Volume:

Volume 71, Number 5

Publisher:

, Pages 848-+

Type of Work:

Article | Post-print: After Peer Review

Abstract:

A ten-eleven translocation (TET) ortholog exists as a DNA N 6 -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. A DNA N 6 -methyladenine (6mA) demethylase (DMAD) was found in Drosophila to actively remove 6mA. Yao et al. demonstrate that DMAD depletion in neurons leads to impaired neurodevelopment accompanied by 6mA accumulation. DMAD and 6mA epigenetically modulate a group of neuronal genes by coordinating with the Trithorax and Polycomb histone modifiers.

Copyright information:

© 2018 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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