Widespread adenine N6-methylation of active genes in fungi.

Authors: Mondo, Stephen J and Dannebaum, Richard O and Kuo, Rita C and Louie, Katherine B and Bewick, Adam J and LaButti, Kurt and Haridas, Sajeet and Kuo, Alan and Salamov, Asaf and Ahrendt, Steven R and Lau, Rebecca and Bowen, Benjamin P and Lipzen, Anna and Sullivan, William and Andreopoulos, Bill B and Clum, Alicia and Lindquist, Erika and Daum, Christopher and Northen, Trent R and Kunde-Ramamoorthy, Govindarajan and Schmitz, Robert J and Gryganskyi, Andrii and Culley, David and Magnuson, Jon and James, Timothy Y and O'Malley, Michelle A and Stajich, Jason E and Spatafora, Joseph W and Visel, Axel and Grigoriev, Igor V

N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. Here we report that abundant 6mA is associated with transcriptionally active genes in early-diverging fungal lineages. Using single-molecule long-read sequencing of 16 diverse fungal genomes, we observed that up to 2.8% of all adenines were methylated in early-diverging fungi, far exceeding levels observed in other eukaryotes and more derived fungi. 6mA occurred symmetrically at ApT dinucleotides and was concentrated in dense methylated adenine clusters surrounding the transcriptional start sites of expressed genes; its distribution was inversely correlated with that of 5-methylcytosine. Our results show a striking contrast in the genomic distributions of 6mA and 5-methylcytosine and reinforce a distinct role for 6mA as a gene-expression-associated epigenomic mark in eukaryotes.

Journal: Nature genetics
DOI: 10.1038/ng.3859
Year: 2017

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