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Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue

Despite recent evidence that 5-hydroxymethylcytosine (5hmC) possesses roles in gene regulation distinct from 5-methylcytosine (5mC), relatively little is known regarding the functions of 5hmC in mammalian tissues. To address this issue, we utilized an approach combining both paired bisulfite (BS) an...

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Autores principales: Wilkins, Owen M., Johnson, Kevin C., Houseman, E. Andres, King, Jessica E., Marsit, Carmen J., Christensen, Brock C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153548/
https://www.ncbi.nlm.nih.gov/pubmed/31842685
http://dx.doi.org/10.1080/15592294.2019.1695332
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author Wilkins, Owen M.
Johnson, Kevin C.
Houseman, E. Andres
King, Jessica E.
Marsit, Carmen J.
Christensen, Brock C.
author_facet Wilkins, Owen M.
Johnson, Kevin C.
Houseman, E. Andres
King, Jessica E.
Marsit, Carmen J.
Christensen, Brock C.
author_sort Wilkins, Owen M.
collection PubMed
description Despite recent evidence that 5-hydroxymethylcytosine (5hmC) possesses roles in gene regulation distinct from 5-methylcytosine (5mC), relatively little is known regarding the functions of 5hmC in mammalian tissues. To address this issue, we utilized an approach combining both paired bisulfite (BS) and oxidative bisulfite (oxBS) DNA treatment, to resolve genome-wide patterns of 5hmC and 5mC in normal breast tissue from disease-free women. Although less abundant than 5mC, 5hmC was differentially distributed, and consistently enriched among breast-specific enhancers and transcriptionally active chromatin. In contrast, regulatory regions associated with transcriptional inactivity, such as heterochromatin and repressed Polycomb regions, were relatively depleted of 5hmC. Gene regions containing abundant 5hmC were significantly associated with lactate oxidation, immune cell function, and prolactin signaling pathways. Furthermore, genes containing abundant 5hmC were enriched among those actively transcribed in normal breast tissue. Finally, in independent data sets, normal breast tissue 5hmC was significantly enriched among CpG loci demonstrated to have altered methylation in pre-invasive breast cancer and invasive breast tumors. Primarily, our findings identify genomic loci containing abundant 5hmC in breast tissues and provide a genome-wide map of nucleotide-level 5hmC in normal breast tissue. Additionally, these data suggest 5hmC may participate in gene regulatory programs that are dysregulated during breast-related carcinogenesis.
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spelling pubmed-71535482020-04-16 Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue Wilkins, Owen M. Johnson, Kevin C. Houseman, E. Andres King, Jessica E. Marsit, Carmen J. Christensen, Brock C. Epigenetics Research Paper Despite recent evidence that 5-hydroxymethylcytosine (5hmC) possesses roles in gene regulation distinct from 5-methylcytosine (5mC), relatively little is known regarding the functions of 5hmC in mammalian tissues. To address this issue, we utilized an approach combining both paired bisulfite (BS) and oxidative bisulfite (oxBS) DNA treatment, to resolve genome-wide patterns of 5hmC and 5mC in normal breast tissue from disease-free women. Although less abundant than 5mC, 5hmC was differentially distributed, and consistently enriched among breast-specific enhancers and transcriptionally active chromatin. In contrast, regulatory regions associated with transcriptional inactivity, such as heterochromatin and repressed Polycomb regions, were relatively depleted of 5hmC. Gene regions containing abundant 5hmC were significantly associated with lactate oxidation, immune cell function, and prolactin signaling pathways. Furthermore, genes containing abundant 5hmC were enriched among those actively transcribed in normal breast tissue. Finally, in independent data sets, normal breast tissue 5hmC was significantly enriched among CpG loci demonstrated to have altered methylation in pre-invasive breast cancer and invasive breast tumors. Primarily, our findings identify genomic loci containing abundant 5hmC in breast tissues and provide a genome-wide map of nucleotide-level 5hmC in normal breast tissue. Additionally, these data suggest 5hmC may participate in gene regulatory programs that are dysregulated during breast-related carcinogenesis. Taylor & Francis 2019-12-16 /pmc/articles/PMC7153548/ /pubmed/31842685 http://dx.doi.org/10.1080/15592294.2019.1695332 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Paper
Wilkins, Owen M.
Johnson, Kevin C.
Houseman, E. Andres
King, Jessica E.
Marsit, Carmen J.
Christensen, Brock C.
Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
title Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
title_full Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
title_fullStr Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
title_full_unstemmed Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
title_short Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
title_sort genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153548/
https://www.ncbi.nlm.nih.gov/pubmed/31842685
http://dx.doi.org/10.1080/15592294.2019.1695332
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