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Global analysis of cytosine and adenine DNA modifications across the tree of life

Interpreting the function and metabolism of enzymatic DNA modifications requires both position-specific and global quantities. Sequencing-based techniques that deliver the former have become broadly accessible, but analytical methods for the global quantification of DNA modifications have thus far b...

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Autores principales: Varma, Sreejith Jayasree, Calvani, Enrica, Grüning, Nana-Maria, Messner, Christoph B, Grayson, Nicholas, Capuano, Floriana, Mülleder, Michael, Ralser, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333990/
https://www.ncbi.nlm.nih.gov/pubmed/35900202
http://dx.doi.org/10.7554/eLife.81002
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author Varma, Sreejith Jayasree
Calvani, Enrica
Grüning, Nana-Maria
Messner, Christoph B
Grayson, Nicholas
Capuano, Floriana
Mülleder, Michael
Ralser, Markus
author_facet Varma, Sreejith Jayasree
Calvani, Enrica
Grüning, Nana-Maria
Messner, Christoph B
Grayson, Nicholas
Capuano, Floriana
Mülleder, Michael
Ralser, Markus
author_sort Varma, Sreejith Jayasree
collection PubMed
description Interpreting the function and metabolism of enzymatic DNA modifications requires both position-specific and global quantities. Sequencing-based techniques that deliver the former have become broadly accessible, but analytical methods for the global quantification of DNA modifications have thus far been applied mostly to individual problems. We established a mass spectrometric method for the sensitive and accurate quantification of multiple enzymatic DNA modifications. Then, we isolated DNA from 124 archean, bacterial, fungal, plant, and mammalian species, and several tissues and created a resource of global DNA modification quantities. Our dataset provides insights into the general nature of enzymatic DNA modifications, reveals unique biological cases, and provides complementary quantitative information to normalize and assess the accuracy of sequencing-based detection of DNA modifications. We report that only three of the studied DNA modifications, methylcytosine (5mdC), methyladenine (N6mdA) and hydroxymethylcytosine (5hmdC), were detected above a picomolar detection limit across species, and dominated in higher eukaryotes (5mdC), in bacteria (N6mdA), or the vertebrate central nervous systems (5hmdC). All three modifications were detected simultaneously in only one of the tested species, Raphanus sativus. In contrast, these modifications were either absent or detected only at trace quantities, across all yeasts and insect genomes studied. Further, we reveal interesting biological cases. For instance, in Allium cepa, Helianthus annuus, or Andropogon gerardi, more than 35% of cytosines were methylated. Additionally, next to the mammlian CNS, 5hmdC was also detected in plants like Lepidium sativum and was found on 8% of cytosines in the Garra barreimiae brain samples. Thus, identifying unexpected levels of DNA modifications in several wild species, our resource underscores the need to address biological diversity for studying DNA modifications.
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spelling pubmed-93339902022-07-29 Global analysis of cytosine and adenine DNA modifications across the tree of life Varma, Sreejith Jayasree Calvani, Enrica Grüning, Nana-Maria Messner, Christoph B Grayson, Nicholas Capuano, Floriana Mülleder, Michael Ralser, Markus eLife Biochemistry and Chemical Biology Interpreting the function and metabolism of enzymatic DNA modifications requires both position-specific and global quantities. Sequencing-based techniques that deliver the former have become broadly accessible, but analytical methods for the global quantification of DNA modifications have thus far been applied mostly to individual problems. We established a mass spectrometric method for the sensitive and accurate quantification of multiple enzymatic DNA modifications. Then, we isolated DNA from 124 archean, bacterial, fungal, plant, and mammalian species, and several tissues and created a resource of global DNA modification quantities. Our dataset provides insights into the general nature of enzymatic DNA modifications, reveals unique biological cases, and provides complementary quantitative information to normalize and assess the accuracy of sequencing-based detection of DNA modifications. We report that only three of the studied DNA modifications, methylcytosine (5mdC), methyladenine (N6mdA) and hydroxymethylcytosine (5hmdC), were detected above a picomolar detection limit across species, and dominated in higher eukaryotes (5mdC), in bacteria (N6mdA), or the vertebrate central nervous systems (5hmdC). All three modifications were detected simultaneously in only one of the tested species, Raphanus sativus. In contrast, these modifications were either absent or detected only at trace quantities, across all yeasts and insect genomes studied. Further, we reveal interesting biological cases. For instance, in Allium cepa, Helianthus annuus, or Andropogon gerardi, more than 35% of cytosines were methylated. Additionally, next to the mammlian CNS, 5hmdC was also detected in plants like Lepidium sativum and was found on 8% of cytosines in the Garra barreimiae brain samples. Thus, identifying unexpected levels of DNA modifications in several wild species, our resource underscores the need to address biological diversity for studying DNA modifications. eLife Sciences Publications, Ltd 2022-07-28 /pmc/articles/PMC9333990/ /pubmed/35900202 http://dx.doi.org/10.7554/eLife.81002 Text en © 2022, Varma, Calvani et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Varma, Sreejith Jayasree
Calvani, Enrica
Grüning, Nana-Maria
Messner, Christoph B
Grayson, Nicholas
Capuano, Floriana
Mülleder, Michael
Ralser, Markus
Global analysis of cytosine and adenine DNA modifications across the tree of life
title Global analysis of cytosine and adenine DNA modifications across the tree of life
title_full Global analysis of cytosine and adenine DNA modifications across the tree of life
title_fullStr Global analysis of cytosine and adenine DNA modifications across the tree of life
title_full_unstemmed Global analysis of cytosine and adenine DNA modifications across the tree of life
title_short Global analysis of cytosine and adenine DNA modifications across the tree of life
title_sort global analysis of cytosine and adenine dna modifications across the tree of life
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333990/
https://www.ncbi.nlm.nih.gov/pubmed/35900202
http://dx.doi.org/10.7554/eLife.81002
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