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A diverse epigenetic landscape at human exons with implication for expression

Singer, Meromit and Kosti, Idit and Pachter, Lior and Mandel-Gutfreund, Yael (2015) A diverse epigenetic landscape at human exons with implication for expression. Nucleic Acids Research, 43 (7). pp. 3498-3508. ISSN 0305-1048. PMCID PMC4402514. doi:10.1093/nar/gkv153. https://resolver.caltech.edu/CaltechAUTHORS:20170303-133948010

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Abstract

DNA methylation is an important epigenetic marker associated with gene expression regulation in eukaryotes. While promoter methylation is relatively well characterized, the role of intragenic DNA methylation remains unclear. Here, we investigated the relationship of DNA methylation at exons and flanking introns with gene expression and histone modifications generated from a human fibroblast cell-line and primary B cells. Consistent with previous work we found that intragenic methylation is positively correlated with gene expression and that exons are more highly methylated than their neighboring intronic environment. Intriguingly, in this study we identified a unique subset of hypomethylated exons that demonstrate significantly lower methylation levels than their surrounding introns. Furthermore, we observed a negative correlation between exon methylation and the density of the majority of histone modifications. Specifically, we demonstrate that hypo-methylated exons at highly expressed genes are associated with open chromatin and have a characteristic histone code comprised of significantly high levels of histone markings. Overall, our comprehensive analysis of the human exome supports the presence of regulatory hypomethylated exons in protein coding genes. In particular our results reveal a previously unrecognized diverse and complex role of the epigenetic landscape within the gene body.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1093/nar/gkv153DOIArticle
https://academic.oup.com/nar/article/43/7/3498/2414327/A-diverse-epigenetic-landscape-at-human-exons-withPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402514/PubMed CentralArticle
ORCID:
AuthorORCID
Pachter, Lior0000-0002-9164-6231
Additional Information:© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received May 19, 2014; Revised January 31, 2015; Accepted February 16, 2015. We would like to thank Asaf Hellman and Dvir Aran for helpful discussions. FUNDING: Israeli Science Foundation [1623/12 to Y.M.G.]. Funding for open access charge: Israeli Science Foundation [1623/12 to Y.M.G.]. Conflict of interest statement. None declared.
Funders:
Funding AgencyGrant Number
Israel Science Foundation1623/12
Subject Keywords:dna methylation; exons; genes; histones; introns; methylation; epigenetics
Issue or Number:7
PubMed Central ID:PMC4402514
DOI:10.1093/nar/gkv153
Record Number:CaltechAUTHORS:20170303-133948010
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170303-133948010
Official Citation:Meromit Singer, Idit Kosti, Lior Pachter, Yael Mandel-Gutfreund; A diverse epigenetic landscape at human exons with implication for expression. Nucleic Acids Res 2015; 43 (7): 3498-3508. doi: 10.1093/nar/gkv153
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74708
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:03 Mar 2017 23:52
Last Modified:11 Nov 2021 05:29

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