The exploration of N6-deoxyadenosine methylation in mammalian genomes

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.