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Effects of DNA methylation on nucleosome stability

Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells. In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA...

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Autores principales: Collings, Clayton K., Waddell, Peter J., Anderson, John N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597673/
https://www.ncbi.nlm.nih.gov/pubmed/23355616
http://dx.doi.org/10.1093/nar/gks893
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author Collings, Clayton K.
Waddell, Peter J.
Anderson, John N.
author_facet Collings, Clayton K.
Waddell, Peter J.
Anderson, John N.
author_sort Collings, Clayton K.
collection PubMed
description Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells. In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes. The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer. The features that distinguished these nucleosomes from the bulk of the methylation-insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away. These methylation-sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation. The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin.
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spelling pubmed-35976732013-03-15 Effects of DNA methylation on nucleosome stability Collings, Clayton K. Waddell, Peter J. Anderson, John N. Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells. In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes. The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer. The features that distinguished these nucleosomes from the bulk of the methylation-insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away. These methylation-sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation. The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin. Oxford University Press 2013-03 2013-01-25 /pmc/articles/PMC3597673/ /pubmed/23355616 http://dx.doi.org/10.1093/nar/gks893 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Collings, Clayton K.
Waddell, Peter J.
Anderson, John N.
Effects of DNA methylation on nucleosome stability
title Effects of DNA methylation on nucleosome stability
title_full Effects of DNA methylation on nucleosome stability
title_fullStr Effects of DNA methylation on nucleosome stability
title_full_unstemmed Effects of DNA methylation on nucleosome stability
title_short Effects of DNA methylation on nucleosome stability
title_sort effects of dna methylation on nucleosome stability
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597673/
https://www.ncbi.nlm.nih.gov/pubmed/23355616
http://dx.doi.org/10.1093/nar/gks893
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