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5mC and 6mA DNA Methylation in the Fungal Kingdom: From Genome Defense to Epigenetic Regulation

Daniil P Malyshev1, Vasiliy V Belov1, Elizaveta S Gromova1

  • 1Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.

Epigenomes
|June 25, 2026
PubMed

Insights

Fungal DNA methylation, involving cytosine (5mC) and adenine (6mA), shows diverse evolutionary strategies. This review details fungal methyltransferases and demethylases, distinct from mammals, highlighting their roles in genome defense and chromatin regulation.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • DNA methylation is a conserved epigenetic mechanism.
  • Fungi exhibit diverse DNA methylation systems, including cytosine (5mC) and adenine (6mA) modifications.
  • These systems are crucial for genome defense (e.g., repeat-induced point mutation) and chromatin regulation.

Purpose of the Study:

  • To review the mechanisms, targets, and biological functions of fungal DNA methyltransferases and demethylases.
  • To integrate recent advances, including cryo-EM structures and evolutionary analyses.
  • To provide a comprehensive account of DNA methylation across the fungal kingdom.

Main Methods:

  • Review of existing literature on fungal DNA methylation.
  • Incorporation of cryo-electron microscopy (cryo-EM) structural insights.
  • Analysis of gene loss in DNA methyltransferase evolution.
  • Examination of the role of 6mA in early-diverging fungal lineages.

Main Results:

  • Fungal methyltransferases (e.g., DIM-2, RID, DNMT5) and demethylases (Dmt1, CcTet) are distinct from mammalian counterparts.
  • DNA methylation in fungi serves roles in transposon silencing, genome defense (RIP), and potentially antiviral defense.
  • Adenine methylation (6mA) is emerging as a significant regulatory mark in early-diverging fungi.

Conclusions:

  • Fungal DNA methylation systems display remarkable evolutionary diversity and distinct molecular mechanisms.
  • Understanding these systems offers insights into epigenetic inheritance and genome evolution.
  • This review consolidates current knowledge, highlighting 6mA as a key regulatory mark in specific fungal lineages.
Keywords:
5-methylcytosineDNA methylationN6-methyladeninefungal epigenomicsrepeat-induced point mutation

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