Cargando…
Links between DNA methylation and nucleosome occupancy in the human genome
BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387343/ https://www.ncbi.nlm.nih.gov/pubmed/28413449 http://dx.doi.org/10.1186/s13072-017-0125-5 |
_version_ | 1782520928188497920 |
---|---|
author | Collings, Clayton K. Anderson, John N. |
author_facet | Collings, Clayton K. Anderson, John N. |
author_sort | Collings, Clayton K. |
collection | PubMed |
description | BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome. RESULTS: The results demonstrated that increasing methylated CpG density is correlated with nucleosome occupancy in the total genome and within nearly all subgenomic regions. Features with elevated methylated CpG density such as exons, SINE-Alu sequences, H3K36-trimethylated peaks, and methylated CpG islands are among the highest nucleosome occupied elements in the genome, while some of the lowest occupancies are displayed by unmethylated CpG islands and unmethylated transcription factor binding sites. Additionally, outside of CpG islands, the density of CpGs within nucleosomes was shown to be important for the nucleosomal location of DNA methylation with low CpG frequencies favoring linker methylation and high CpG frequencies favoring core particle methylation. Prominent exceptions to the correlations between methylated CpG density and nucleosome occupancy include CpG islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and these modifications, along with DNA methylation, distinguish the major silencing mechanisms of the human epigenome. CONCLUSIONS: Thus, the relationship between DNA methylation and nucleosome occupancy is influenced by the density of methylated CpG dinucleotides and by other epigenomic components in chromatin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-017-0125-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5387343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53873432017-04-14 Links between DNA methylation and nucleosome occupancy in the human genome Collings, Clayton K. Anderson, John N. Epigenetics Chromatin Research BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome. RESULTS: The results demonstrated that increasing methylated CpG density is correlated with nucleosome occupancy in the total genome and within nearly all subgenomic regions. Features with elevated methylated CpG density such as exons, SINE-Alu sequences, H3K36-trimethylated peaks, and methylated CpG islands are among the highest nucleosome occupied elements in the genome, while some of the lowest occupancies are displayed by unmethylated CpG islands and unmethylated transcription factor binding sites. Additionally, outside of CpG islands, the density of CpGs within nucleosomes was shown to be important for the nucleosomal location of DNA methylation with low CpG frequencies favoring linker methylation and high CpG frequencies favoring core particle methylation. Prominent exceptions to the correlations between methylated CpG density and nucleosome occupancy include CpG islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and these modifications, along with DNA methylation, distinguish the major silencing mechanisms of the human epigenome. CONCLUSIONS: Thus, the relationship between DNA methylation and nucleosome occupancy is influenced by the density of methylated CpG dinucleotides and by other epigenomic components in chromatin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-017-0125-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-04-11 /pmc/articles/PMC5387343/ /pubmed/28413449 http://dx.doi.org/10.1186/s13072-017-0125-5 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 | Research Collings, Clayton K. Anderson, John N. Links between DNA methylation and nucleosome occupancy in the human genome |
title | Links between DNA methylation and nucleosome occupancy in the human genome |
title_full | Links between DNA methylation and nucleosome occupancy in the human genome |
title_fullStr | Links between DNA methylation and nucleosome occupancy in the human genome |
title_full_unstemmed | Links between DNA methylation and nucleosome occupancy in the human genome |
title_short | Links between DNA methylation and nucleosome occupancy in the human genome |
title_sort | links between dna methylation and nucleosome occupancy in the human genome |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387343/ https://www.ncbi.nlm.nih.gov/pubmed/28413449 http://dx.doi.org/10.1186/s13072-017-0125-5 |
work_keys_str_mv | AT collingsclaytonk linksbetweendnamethylationandnucleosomeoccupancyinthehumangenome AT andersonjohnn linksbetweendnamethylationandnucleosomeoccupancyinthehumangenome |