Background: Epigenetic modifications have been evidenced to participate in eukaryotic
stem cell fate decision. Among the most studied, 5-methylcytosine (m5C) and its derivatives are wellestablished
epigenetic codes that play important roles in stem cell pluripotency and differentiation.
Based on improved detection techniques, recent studies have succeeded in defining N6-adenine methylation
(m6A) in eukaryotic DNA and RNA. The abundant m6A methylation in RNA was shown to be
involved in multiple cellular metabolisms while the presence and functional potential of DNA m6A
methylation in different species advanced our knowledge in the m6A-mediated biological processes.
Conclusion: m6A modification has been observed during embryogenesis and has been proposed to
fine-tune stem cell regulation. The m6A methyltransferases and demethylases work together to control
the dynamic state of m6A marks in genomic DNA and RNA to ensure proper cell fate transition and
determination, which are vital to the development and survival of eukaryotes.