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bioRxiv · 10.1101/2023.03.27.534452

A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation

Grub, L. K.·Held, J. P.·Hansen, T. J.·Schaffner, S. H.·Canter, M. R.·Malagise, E. M.·Patel, M. R.
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Abstract

Epigenetic modifications provide powerful means for transmitting information from parent to progeny. As a maternally inherited genome that encodes essential components of the electron transport chain, the mitochondrial genome (mtDNA) is ideally positioned to serve as a conduit for the transgenerational transmission of metabolic information. Here, we provide evidence that mtDNA of C. elegans contains the epigenetic mark N6-methyldeoxyadenosine (6mA). Bioinformatic analysis of SMRT sequencing data and methylated DNA IP sequencing data reveal that C. elegans mtDNA is methylated at high levels in a site-specific manner. We further confirmed that mtDNA contains 6mA by leveraging highly specific anti-6mA antibodies. Additionally, we find that mtDNA methylation is dynamically regulated in response to antimycin, a mitochondrial stressor. Further, 6mA is increased in nmad-1 mutants and is accompanied by a significant decrease in mtDNA copy number. Our discovery paves the way for future studies to investigate the regulation and inheritance of mitochondrial epigenetics.

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Grub, L. K., Held, J. P., Hansen, T. J., Schaffner, S. H., Canter, M. R., Malagise, E. M., Patel, M. R.. 2023-03-29. A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation. https://doi.org/10.1101/2023.03.27.534452

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