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Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice

BACKGROUND: Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymethylcytosine (5-hmC), in both stem cells and post-mito...

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Autores principales: Chopra, Pankaj, Papale, Ligia A, White, Andrew T J, Hatch, Andrea, Brown, Ryan M, Garthwaite, Mark A, Roseboom, Patrick H, Golos, Thaddeus G, Warren, Stephen T, Alisch, Reid S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930898/
https://www.ncbi.nlm.nih.gov/pubmed/24524199
http://dx.doi.org/10.1186/1471-2164-15-131
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author Chopra, Pankaj
Papale, Ligia A
White, Andrew T J
Hatch, Andrea
Brown, Ryan M
Garthwaite, Mark A
Roseboom, Patrick H
Golos, Thaddeus G
Warren, Stephen T
Alisch, Reid S
author_facet Chopra, Pankaj
Papale, Ligia A
White, Andrew T J
Hatch, Andrea
Brown, Ryan M
Garthwaite, Mark A
Roseboom, Patrick H
Golos, Thaddeus G
Warren, Stephen T
Alisch, Reid S
author_sort Chopra, Pankaj
collection PubMed
description BACKGROUND: Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymethylcytosine (5-hmC), in both stem cells and post-mitotic neurons, raises new questions as to the role of this base in mediating epigenetic effects. Genomic studies of these marks using model systems are limited, particularly with array-based tools, because the standard method of detecting DNA methylation cannot distinguish between 5-mC and 5-hmC and most methods have been developed to only survey the human genome. RESULTS: We show that non-human data generated using the optimization of a widely used human DNA methylation array, designed only to detect 5-mC, reproducibly distinguishes tissue types within and between chimpanzee, rhesus, and mouse, with correlations near the human DNA level (R(2) > 0.99). Genome-wide methylation analysis, using this approach, reveals 6,102 differentially methylated loci between rhesus placental and fetal tissues with pathways analysis significantly overrepresented for developmental processes. Restricting the analysis to oncogenes and tumor suppressor genes finds 76 differentially methylated loci, suggesting that rhesus placental tissue carries a cancer epigenetic signature. Similarly, adapting the assay to detect 5-hmC finds highly reproducible 5-hmC levels within human, rhesus, and mouse brain tissue that is species-specific with a hierarchical abundance among the three species (human > rhesus >> mouse). Annotation of 5-hmC with respect to gene structure reveals a significant prevalence in the 3'UTR and an association with chromatin-related ontological terms, suggesting an epigenetic feedback loop mechanism for 5-hmC. CONCLUSIONS: Together, these data show that this array-based methylation assay is generalizable to all mammals for the detection of both 5-mC and 5-hmC, greatly improving the utility of mammalian model systems to study the role of epigenetics in human health, disease, and evolution.
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spelling pubmed-39308982014-02-22 Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice Chopra, Pankaj Papale, Ligia A White, Andrew T J Hatch, Andrea Brown, Ryan M Garthwaite, Mark A Roseboom, Patrick H Golos, Thaddeus G Warren, Stephen T Alisch, Reid S BMC Genomics Methodology Article BACKGROUND: Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymethylcytosine (5-hmC), in both stem cells and post-mitotic neurons, raises new questions as to the role of this base in mediating epigenetic effects. Genomic studies of these marks using model systems are limited, particularly with array-based tools, because the standard method of detecting DNA methylation cannot distinguish between 5-mC and 5-hmC and most methods have been developed to only survey the human genome. RESULTS: We show that non-human data generated using the optimization of a widely used human DNA methylation array, designed only to detect 5-mC, reproducibly distinguishes tissue types within and between chimpanzee, rhesus, and mouse, with correlations near the human DNA level (R(2) > 0.99). Genome-wide methylation analysis, using this approach, reveals 6,102 differentially methylated loci between rhesus placental and fetal tissues with pathways analysis significantly overrepresented for developmental processes. Restricting the analysis to oncogenes and tumor suppressor genes finds 76 differentially methylated loci, suggesting that rhesus placental tissue carries a cancer epigenetic signature. Similarly, adapting the assay to detect 5-hmC finds highly reproducible 5-hmC levels within human, rhesus, and mouse brain tissue that is species-specific with a hierarchical abundance among the three species (human > rhesus >> mouse). Annotation of 5-hmC with respect to gene structure reveals a significant prevalence in the 3'UTR and an association with chromatin-related ontological terms, suggesting an epigenetic feedback loop mechanism for 5-hmC. CONCLUSIONS: Together, these data show that this array-based methylation assay is generalizable to all mammals for the detection of both 5-mC and 5-hmC, greatly improving the utility of mammalian model systems to study the role of epigenetics in human health, disease, and evolution. BioMed Central 2014-02-13 /pmc/articles/PMC3930898/ /pubmed/24524199 http://dx.doi.org/10.1186/1471-2164-15-131 Text en Copyright © 2014 Chopra et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Chopra, Pankaj
Papale, Ligia A
White, Andrew T J
Hatch, Andrea
Brown, Ryan M
Garthwaite, Mark A
Roseboom, Patrick H
Golos, Thaddeus G
Warren, Stephen T
Alisch, Reid S
Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice
title Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice
title_full Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice
title_fullStr Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice
title_full_unstemmed Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice
title_short Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice
title_sort array-based assay detects genome-wide 5-mc and 5-hmc in the brains of humans, non-human primates, and mice
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930898/
https://www.ncbi.nlm.nih.gov/pubmed/24524199
http://dx.doi.org/10.1186/1471-2164-15-131
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