The exploration of N6-deoxyadenosine methylation in mammalian genomes

Protein Cell. 2021 Oct;12(10):756-768. doi: 10.1007/s13238-021-00866-3. Epub 2021 Aug 17.


N6-methyladenine (N6-mA, m6dA, or 6mA), a prevalent DNA modification in prokaryotes, has recently been identified in higher eukaryotes, including mammals. Although 6mA has been well-studied in prokaryotes, the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood. Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes, from transposable-element suppression to environmental stress response. Here, we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes, predominantly mammals.

Keywords: DNA N6-methyladenine (6mA); mammalian DNA modification; non-canonical mammalian DNA methylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / metabolism
  • Aminopyrine N-Demethylase / genetics
  • Aminopyrine N-Demethylase / metabolism
  • Animals
  • Chromatography, High Pressure Liquid
  • DNA / genetics
  • DNA / metabolism*
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair*
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Genome*
  • Heterochromatin / chemistry
  • Heterochromatin / metabolism
  • Humans
  • Immunoblotting
  • Mammals
  • Mass Spectrometry


  • Heterochromatin
  • DNA
  • Aminopyrine N-Demethylase
  • DNA Modification Methylases
  • Adenine
  • 6-methyladenine