N6-methyladenine DNA modification in Drosophila

Cell. 2015 May 7;161(4):893-906. doi: 10.1016/j.cell.2015.04.018. Epub 2015 Apr 30.

Abstract

DNA N(6)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / metabolism
  • Amino Acid Sequence
  • Animals
  • DNA Methylation*
  • DNA Transposable Elements
  • Drosophila / embryology
  • Drosophila / enzymology
  • Drosophila / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Molecular Sequence Data
  • Ovary / metabolism
  • Sequence Alignment
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / metabolism

Substances

  • DNA Transposable Elements
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)
  • Adenine
  • 6-methyladenine

Associated data

  • SRA/SRP055483