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DNA methylation in blood—Potential to provide new insights into cell biology

Epigenetics plays a fundamental role in cellular development and differentiation; epigenetic mechanisms, such as DNA methylation, are involved in gene regulation and the exquisite nuance of expression changes seen in the journey from pluripotency to final differentiation. Thus, DNA methylation as a...

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Autores principales: Macartney-Coxson, Donia, Cameron, Alanna M., Clapham, Jane, Benton, Miles C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641429/
https://www.ncbi.nlm.nih.gov/pubmed/33147241
http://dx.doi.org/10.1371/journal.pone.0241367
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author Macartney-Coxson, Donia
Cameron, Alanna M.
Clapham, Jane
Benton, Miles C.
author_facet Macartney-Coxson, Donia
Cameron, Alanna M.
Clapham, Jane
Benton, Miles C.
author_sort Macartney-Coxson, Donia
collection PubMed
description Epigenetics plays a fundamental role in cellular development and differentiation; epigenetic mechanisms, such as DNA methylation, are involved in gene regulation and the exquisite nuance of expression changes seen in the journey from pluripotency to final differentiation. Thus, DNA methylation as a marker of cell identify has the potential to reveal new insights into cell biology. We mined publicly available DNA methylation data with a machine-learning approach to identify differentially methylated loci between different white blood cell types. We then interrogated the DNA methylation and mRNA expression of candidate loci in CD4(+), CD8(+), CD14(+), CD19(+) and CD56(+) fractions from 12 additional, independent healthy individuals (6 male, 6 female). ‘Classic’ immune cell markers such as CD8 and CD19 showed expected methylation/expression associations fitting with established dogma that hypermethylation is associated with the repression of gene expression. We also observed large differential methylation at loci which are not established immune cell markers; some of these loci showed inverse correlations between methylation and mRNA expression (such as PARK2, DCP2). Furthermore, we validated these observations further in publicly available DNA methylation and RNA sequencing datasets. Our results highlight the value of mining publicly available data, the utility of DNA methylation as a discriminatory marker and the potential value of DNA methylation to provide additional insights into cell biology and developmental processes.
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spelling pubmed-76414292020-11-16 DNA methylation in blood—Potential to provide new insights into cell biology Macartney-Coxson, Donia Cameron, Alanna M. Clapham, Jane Benton, Miles C. PLoS One Research Article Epigenetics plays a fundamental role in cellular development and differentiation; epigenetic mechanisms, such as DNA methylation, are involved in gene regulation and the exquisite nuance of expression changes seen in the journey from pluripotency to final differentiation. Thus, DNA methylation as a marker of cell identify has the potential to reveal new insights into cell biology. We mined publicly available DNA methylation data with a machine-learning approach to identify differentially methylated loci between different white blood cell types. We then interrogated the DNA methylation and mRNA expression of candidate loci in CD4(+), CD8(+), CD14(+), CD19(+) and CD56(+) fractions from 12 additional, independent healthy individuals (6 male, 6 female). ‘Classic’ immune cell markers such as CD8 and CD19 showed expected methylation/expression associations fitting with established dogma that hypermethylation is associated with the repression of gene expression. We also observed large differential methylation at loci which are not established immune cell markers; some of these loci showed inverse correlations between methylation and mRNA expression (such as PARK2, DCP2). Furthermore, we validated these observations further in publicly available DNA methylation and RNA sequencing datasets. Our results highlight the value of mining publicly available data, the utility of DNA methylation as a discriminatory marker and the potential value of DNA methylation to provide additional insights into cell biology and developmental processes. Public Library of Science 2020-11-04 /pmc/articles/PMC7641429/ /pubmed/33147241 http://dx.doi.org/10.1371/journal.pone.0241367 Text en © 2020 Macartney-Coxson et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Macartney-Coxson, Donia
Cameron, Alanna M.
Clapham, Jane
Benton, Miles C.
DNA methylation in blood—Potential to provide new insights into cell biology
title DNA methylation in blood—Potential to provide new insights into cell biology
title_full DNA methylation in blood—Potential to provide new insights into cell biology
title_fullStr DNA methylation in blood—Potential to provide new insights into cell biology
title_full_unstemmed DNA methylation in blood—Potential to provide new insights into cell biology
title_short DNA methylation in blood—Potential to provide new insights into cell biology
title_sort dna methylation in blood—potential to provide new insights into cell biology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641429/
https://www.ncbi.nlm.nih.gov/pubmed/33147241
http://dx.doi.org/10.1371/journal.pone.0241367
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