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Minimal detection and low biological fluctuation of mitochondrial CpG methylation at the single-molecule level

View ORCID ProfileChloe Goldsmith, View ORCID ProfileJesús Rafael Rodríguez-Aguilera, Ines El-Rifai, Adrien Jarretier, Valérie Hervieu, View ORCID ProfileVictoria Chagoya de Sánchez, Robert Dante, View ORCID ProfileGabriel Ichim, View ORCID ProfileHector Hernandez-Vargas
doi: https://doi.org/10.1101/2020.09.14.296269
Chloe Goldsmith
1Department of Tumor Escape, Resistance and Immunity. TGF-beta and immuno-regulation Team. Cancer Research Centre of Lyon (CRCL), Inserm U 1052, CNRS UMR 5286, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon CEDEX 08, France
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  • For correspondence: chloe.goldsmith@inserm.fr hector.hernandez-vargas@lyon.unicancer.fr
Jesús Rafael Rodríguez-Aguilera
2Department of Cellular Biology and Development, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, Ciudad Universitaria, Coyoacán 04510, Cd. Mx., Mexico
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Ines El-Rifai
1Department of Tumor Escape, Resistance and Immunity. TGF-beta and immuno-regulation Team. Cancer Research Centre of Lyon (CRCL), Inserm U 1052, CNRS UMR 5286, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon CEDEX 08, France
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Adrien Jarretier
1Department of Tumor Escape, Resistance and Immunity. TGF-beta and immuno-regulation Team. Cancer Research Centre of Lyon (CRCL), Inserm U 1052, CNRS UMR 5286, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon CEDEX 08, France
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Valérie Hervieu
3Department of Surgical Pathology, Hospices Civils de Lyon, Groupement Hospitalier Est, Lyon, France
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Victoria Chagoya de Sánchez
2Department of Cellular Biology and Development, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, Ciudad Universitaria, Coyoacán 04510, Cd. Mx., Mexico
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Robert Dante
4Dependence Receptors Cancer and Development Laboratory, Department of Signaling of Tumoral Escape. Cancer Research. Center of Lyon (CRCL), Inserm U 1052, CNRS UMR 5286, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon CEDEX 08, France
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Gabriel Ichim
5Cancer Cell Death Laboratory, Part of LabEx DEVweCAN, Université de Lyon, Lyon, France. Cancer Research Centre of Lyon (CRCL), Inserm U 1052, CNRS UMR 5286, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon CEDEX 08, France
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Hector Hernandez-Vargas
1Department of Tumor Escape, Resistance and Immunity. TGF-beta and immuno-regulation Team. Cancer Research Centre of Lyon (CRCL), Inserm U 1052, CNRS UMR 5286, Université de Lyon, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon CEDEX 08, France
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  • For correspondence: chloe.goldsmith@inserm.fr hector.hernandez-vargas@lyon.unicancer.fr
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Abstract

Cytosine DNA methylation in the CpG context (5mCpG) is associated with the transcriptional status of nuclear DNA. Due to technical limitations, it has been less clear if mitochondrial DNA (mtDNA) is methylated and whether 5mCpG has a regulatory role in this context. The main aim of this work was to develop and validate a novel tool for determining methylation of mtDNA and to corroborate its existence across different biological contexts. Using long-read nanopore sequencing we found low levels of CpG methylation (with few exceptions) and little variation across biological processes: differentiation, oxidative stress, and cancer. 5mCpG was overall higher in tissues compared to cell lines, with small additional variation between cell lines of different origin. Although we do show several significant changes in all these conditions, 5mCpG is unlikely to play a major role in defining the transcriptional status of mitochondrial genes.

Competing Interest Statement

C.G. and H.H.-V. have received travel and accommodation support to attend conferences for Oxford Nanopore Technology. The authors declare that they have no additional competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 14, 2020.
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Minimal detection and low biological fluctuation of mitochondrial CpG methylation at the single-molecule level
Chloe Goldsmith, Jesús Rafael Rodríguez-Aguilera, Ines El-Rifai, Adrien Jarretier, Valérie Hervieu, Victoria Chagoya de Sánchez, Robert Dante, Gabriel Ichim, Hector Hernandez-Vargas
bioRxiv 2020.09.14.296269; doi: https://doi.org/10.1101/2020.09.14.296269
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Minimal detection and low biological fluctuation of mitochondrial CpG methylation at the single-molecule level
Chloe Goldsmith, Jesús Rafael Rodríguez-Aguilera, Ines El-Rifai, Adrien Jarretier, Valérie Hervieu, Victoria Chagoya de Sánchez, Robert Dante, Gabriel Ichim, Hector Hernandez-Vargas
bioRxiv 2020.09.14.296269; doi: https://doi.org/10.1101/2020.09.14.296269

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