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

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 transgeneratio...

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Autores principales: Grub, Lantana K., Held, James P., Hansen, Tyler J., Schaffner, Samantha H., Canter, Marleigh R., Malagise, Evi M., Patel, Maulik R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081187/
https://www.ncbi.nlm.nih.gov/pubmed/37034795
http://dx.doi.org/10.1101/2023.03.27.534452
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author Grub, Lantana K.
Held, James P.
Hansen, Tyler J.
Schaffner, Samantha H.
Canter, Marleigh R.
Malagise, Evi M.
Patel, Maulik R.
author_facet Grub, Lantana K.
Held, James P.
Hansen, Tyler J.
Schaffner, Samantha H.
Canter, Marleigh R.
Malagise, Evi M.
Patel, Maulik R.
author_sort Grub, Lantana K.
collection PubMed
description 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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spelling pubmed-100811872023-04-08 A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation Grub, Lantana K. Held, James P. Hansen, Tyler J. Schaffner, Samantha H. Canter, Marleigh R. Malagise, Evi M. Patel, Maulik R. bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-03-29 /pmc/articles/PMC10081187/ /pubmed/37034795 http://dx.doi.org/10.1101/2023.03.27.534452 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Grub, Lantana K.
Held, James P.
Hansen, Tyler J.
Schaffner, Samantha H.
Canter, Marleigh R.
Malagise, Evi M.
Patel, Maulik R.
A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation
title A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation
title_full A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation
title_fullStr A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation
title_full_unstemmed A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation
title_short A role for N6-methyldeoxyadenosine in C. elegans mitochondrial genome regulation
title_sort role for n6-methyldeoxyadenosine in c. elegans mitochondrial genome regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081187/
https://www.ncbi.nlm.nih.gov/pubmed/37034795
http://dx.doi.org/10.1101/2023.03.27.534452
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