dc.contributor.author | Elliott, G | |
dc.contributor.author | Hong, C | |
dc.contributor.author | Xing, X | |
dc.contributor.author | Zhou, X | |
dc.contributor.author | Li, D | |
dc.contributor.author | Coarfa, C | |
dc.contributor.author | Bell, RJ | |
dc.contributor.author | Maire, CL | |
dc.contributor.author | Ligon, KL | |
dc.contributor.author | Sigaroudinia, M | |
dc.contributor.author | Gascard, P | |
dc.contributor.author | Tlsty, TD | |
dc.contributor.author | Harris, RA | |
dc.contributor.author | Schalkwyk, LC | |
dc.contributor.author | Bilenky, M | |
dc.contributor.author | Mill, J | |
dc.contributor.author | Farnham, PJ | |
dc.contributor.author | Kellis, M | |
dc.contributor.author | Marra, MA | |
dc.contributor.author | Milosavljevic, A | |
dc.contributor.author | Hirst, M | |
dc.contributor.author | Stormo, GD | |
dc.contributor.author | Wang, T | |
dc.contributor.author | Costello, JF | |
dc.date.accessioned | 2016-03-01T10:03:38Z | |
dc.date.issued | 2015-02-18 | |
dc.description.abstract | The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 human primary cell and tissue samples. We report 18,452 intermediate methylation regions located near 36% of genes and enriched at enhancers, exons and DNase I hypersensitivity sites. Intermediate methylation regions average 57% methylation, are predominantly allele-independent and are conserved across individuals and between mouse and human, suggesting a conserved function. These regions have an intermediate level of active chromatin marks and their associated genes have intermediate transcriptional activity. Exonic intermediate methylation correlates with exon inclusion at a level between that of fully methylated and unmethylated exons, highlighting gene context-dependent functions. We conclude that intermediate DNA methylation is a conserved signature of gene regulation and exon usage. | en_GB |
dc.description.sponsorship | We thank collaborators in the Reference Epigenome Mapping Centers (REMC), the Epigenome Data Analysis and Coordination Center and NCBI who have generated and processed data used in this project. We thank Jufang Chang and Jeff Milbrandt for providing mouse cortical neuron samples. We acknowledge support from the NIH Roadmap Epigenomics Program, sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). We thank Theresa Kadlecek and Arthur Weiss for processing blood samples. J.F.C. and T.W.
are supported by NIH grant 5U01ES017154. G.E. is partly supported by the Chancellor’s Graduate Fellowship Program at the Washington University in St Louis. T.W. and G.E. are also supported by NIH Grant R01HG007354, R01HG007175, R01ES024992 and American Cancer Society grant RSG-14-049-01-DMC. J.F.C. is also supported by NIH R01CA169316. | en_GB |
dc.identifier.citation | Nature Communications, 2015, Vol. 6, Article number 6363 | en_GB |
dc.identifier.doi | 10.1038/ncomms7363 | |
dc.identifier.uri | http://hdl.handle.net/10871/20291 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Publishing Group | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/25691127 | en_GB |
dc.rights | This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.title | Intermediate DNA methylation is a conserved signature of genome regulation. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-03-01T10:03:38Z | |
exeter.place-of-publication | England | |
dc.description | Published online | en_GB |
dc.description | Research Support, N.I.H., Extramural | en_GB |
dc.description | Research Support, Non-U.S. Gov't | en_GB |
dc.description | This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms7363 | en_GB |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.journal | Nature Communications | en_GB |