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Symmetric adenine methylation is an essential DNA modification in the early-diverging fungus Rhizopus microsporus

Author

Listed:
  • Carlos Lax

    (Universidad de Murcia)

  • Stephen J. Mondo

    (Lawrence Berkeley National Laboratory
    Colorado State University
    Lawrence Berkeley National Laboratory)

  • José F. Martínez

    (Universidad de Murcia)

  • Anna Muszewska

    (Polish Academy of Sciences)

  • Leo A. Baumgart

    (Lawrence Berkeley National Laboratory)

  • José A. Pérez-Ruiz

    (Universidad de Murcia)

  • Pablo Carrillo-Marín

    (Universidad de Murcia)

  • Kurt LaButti

    (Lawrence Berkeley National Laboratory)

  • Anna Lipzen

    (Lawrence Berkeley National Laboratory)

  • Yu Zhang

    (Lawrence Berkeley National Laboratory)

  • Jie Guo

    (Lawrence Berkeley National Laboratory)

  • Vivian Ng

    (Lawrence Berkeley National Laboratory)

  • Eusebio Navarro

    (Universidad de Murcia)

  • Teresa E. Pawlowska

    (Cornell University)

  • Igor V. Grigoriev

    (Lawrence Berkeley National Laboratory
    Lawrence Berkeley National Laboratory
    University of California Berkeley)

  • Francisco E. Nicolás

    (Universidad de Murcia)

  • Victoriano Garre

    (Universidad de Murcia)

Abstract

The discovery of N6-methyladenine (6mA) in eukaryotic genomes, typically found in prokaryotic DNA, has revolutionized epigenetics. Here, we show that symmetric 6mA is essential in the early diverging fungus Rhizopus microsporus, as the absence of the MT-A70 complex (MTA1c) responsible for this modification results in a lethal phenotype. 6mA is present in 70% of the genes, correlating with the presence of H3K4me3 and H2A.Z in open euchromatic regions. This modification is found predominantly in nucleosome linker regions, influencing the nucleosome positioning around the transcription start sites of highly expressed genes. Controlled downregulation of MTA1c reduces symmetric 6mA sites affecting nucleosome positioning and histone modifications, leading to altered gene expression, which is likely the cause of the severe phenotypic changes observed. Our study highlights the indispensable role of the DNA 6mA in a multicellular organism and delineates the mechanisms through which this epigenetic mark regulates gene expression in a eukaryotic genome.

Suggested Citation

  • Carlos Lax & Stephen J. Mondo & José F. Martínez & Anna Muszewska & Leo A. Baumgart & José A. Pérez-Ruiz & Pablo Carrillo-Marín & Kurt LaButti & Anna Lipzen & Yu Zhang & Jie Guo & Vivian Ng & Eusebio , 2025. "Symmetric adenine methylation is an essential DNA modification in the early-diverging fungus Rhizopus microsporus," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59170-x
    DOI: 10.1038/s41467-025-59170-x
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    References listed on IDEAS

    as
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