Symmetric adenine methylation is an essential DNA modification in the early-diverging fungus Rhizopus microsporus
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.
Authors
- Vivian Ng (ORCID: https://orcid.org/0000-0001-8941-6931)
- Victoriano Garre (ORCID: https://orcid.org/0000-0001-7605-1726)
- Igor V. Grigoriev (ORCID: https://orcid.org/0000-0002-3136-8903)
- Stephen J. Mondo (ORCID: https://orcid.org/0000-0001-5797-0647)
- Anna Muszewska (ORCID: https://orcid.org/0000-0002-4578-844X)
- Teresa E. Pawlowska (ORCID: https://orcid.org/0000-0002-1094-2427)
- Yu Zhang (ORCID: https://orcid.org/0000-0003-4495-3447)
- Anna Lipzen (ORCID: https://orcid.org/0000-0003-2293-9329)
- Leo Baumgart (ORCID: https://orcid.org/0000-0002-2773-5897)
- Eusebio Navarro (ORCID: https://orcid.org/0000-0002-3091-4378)
- Pablo Carrillo-Marín
- Francisco E. Nicolás (ORCID: https://orcid.org/0000-0003-3762-5971)
- José Antonio Pérez-Ruiz (ORCID: https://orcid.org/0000-0002-5901-5472)
- Jie Guo (ORCID: https://orcid.org/0000-0001-6104-9957)
- Carlos Lax (ORCID: https://orcid.org/0000-0002-2059-303X)
- Kurt LaButti (ORCID: https://orcid.org/0000-0002-5838-1972)
- José Francisco Martı́nez (ORCID: https://orcid.org/0000-0002-3457-2088)
Institutions
- Lawrence Berkeley National Laboratory (US)
- Joint Genome Institute (US)
- Cornell University (US)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL)
- Universidad de Murcia (ES)
- Colorado State University (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1038/s41467-025-59170-x
- Citations
- 6
- Primary Topic
- Legume Nitrogen Fixing Symbiosis
- Type
- article
- Field-Weighted Citation Impact
- 10.50
Funders
- U.S. Department of Energy
- Joint Genome Institute
- Office of Science
- European Regional Development Fund
- Agencia Estatal de Investigación