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Dynamic DNA methylation across diverse human cell lines and tissues

As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a di...

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Autores principales: Varley, Katherine E., Gertz, Jason, Bowling, Kevin M., Parker, Stephanie L., Reddy, Timothy E., Pauli-Behn, Florencia, Cross, Marie K., Williams, Brian A., Stamatoyannopoulos, John A., Crawford, Gregory E., Absher, Devin M., Wold, Barbara J., Myers, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589544/
https://www.ncbi.nlm.nih.gov/pubmed/23325432
http://dx.doi.org/10.1101/gr.147942.112
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author Varley, Katherine E.
Gertz, Jason
Bowling, Kevin M.
Parker, Stephanie L.
Reddy, Timothy E.
Pauli-Behn, Florencia
Cross, Marie K.
Williams, Brian A.
Stamatoyannopoulos, John A.
Crawford, Gregory E.
Absher, Devin M.
Wold, Barbara J.
Myers, Richard M.
author_facet Varley, Katherine E.
Gertz, Jason
Bowling, Kevin M.
Parker, Stephanie L.
Reddy, Timothy E.
Pauli-Behn, Florencia
Cross, Marie K.
Williams, Brian A.
Stamatoyannopoulos, John A.
Crawford, Gregory E.
Absher, Devin M.
Wold, Barbara J.
Myers, Richard M.
author_sort Varley, Katherine E.
collection PubMed
description As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease.
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spelling pubmed-35895442013-09-01 Dynamic DNA methylation across diverse human cell lines and tissues Varley, Katherine E. Gertz, Jason Bowling, Kevin M. Parker, Stephanie L. Reddy, Timothy E. Pauli-Behn, Florencia Cross, Marie K. Williams, Brian A. Stamatoyannopoulos, John A. Crawford, Gregory E. Absher, Devin M. Wold, Barbara J. Myers, Richard M. Genome Res Resource As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease. Cold Spring Harbor Laboratory Press 2013-03 /pmc/articles/PMC3589544/ /pubmed/23325432 http://dx.doi.org/10.1101/gr.147942.112 Text en © 2013, Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Resource
Varley, Katherine E.
Gertz, Jason
Bowling, Kevin M.
Parker, Stephanie L.
Reddy, Timothy E.
Pauli-Behn, Florencia
Cross, Marie K.
Williams, Brian A.
Stamatoyannopoulos, John A.
Crawford, Gregory E.
Absher, Devin M.
Wold, Barbara J.
Myers, Richard M.
Dynamic DNA methylation across diverse human cell lines and tissues
title Dynamic DNA methylation across diverse human cell lines and tissues
title_full Dynamic DNA methylation across diverse human cell lines and tissues
title_fullStr Dynamic DNA methylation across diverse human cell lines and tissues
title_full_unstemmed Dynamic DNA methylation across diverse human cell lines and tissues
title_short Dynamic DNA methylation across diverse human cell lines and tissues
title_sort dynamic dna methylation across diverse human cell lines and tissues
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589544/
https://www.ncbi.nlm.nih.gov/pubmed/23325432
http://dx.doi.org/10.1101/gr.147942.112
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