biostudies-literatureLax CMinistry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)Narodowe Centrum Nauki (National Science Centre)3843https://www.ebi.ac.uk/biostudies/studies/S-EPMC12019607biostudies-literatureUnknown16(1)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 likNature communicationsSymmetric adenine methylation is an essential DNA modification in the early-diverging fungus Rhizopus microsporus.PMC12019607#2021/41/B/NZ2/02426PID2021-124674NB-I002021/41/B/NZ2/02426Grigoriev IVMartinez JFNg VLaButti KGuo JCarrillo-Marin PPawlowska TEBaumgart LAZhang YMondo SJPerez-Ruiz JANicolas FELax CNavarro ELipzen AMuszewska AGarre VfalseSymmetric 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 lik2025-01-01T00:00:00Z2025 Apr2026-06-02T18:25:05.869Z2026-04-18T03:13:59.036ZS-EPMC120196074026891810.1038/s41467-025-59170-x