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dc.contributor.authorde la Rica, L
dc.contributor.authorDeniz, Ö
dc.contributor.authorCheng, KCL
dc.contributor.authorTodd, CD
dc.contributor.authorCruz, C
dc.contributor.authorHouseley, J
dc.contributor.authorBranco, MR
dc.date.accessioned2016-12-07T10:41:03Z
dc.date.issued2016-11-18
dc.date.issued2016-11-18
dc.date.issued2016-11-18
dc.date.issued2016-11-18
dc.date.submitted2016-11-21T09:02:54.180Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/18153
dc.description.abstractBACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host. RESULTS: We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner. CONCLUSIONS: Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.
dc.description.sponsorshipMRB is a Sir Henry Dale Fellow (101225/Z/13/Z), jointly funded by the Wellcome Trust and the Royal Society. LR and OD have received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 608765. JH is funded by the Wellcome Trust (110216) and CC by the BBSRC.en_US
dc.format.extent234 - ?
dc.languageeng
dc.relation.ispartofGenome Biol
dc.rightsThis 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.
dc.subjectDNA methylation
dc.subjectEmbryonic stem cells
dc.subjectEnhancers
dc.subjectHydroxymethylation
dc.subjectLINE-1
dc.subjectRetrotransposons
dc.subjectTen-eleven translocation enzymes
dc.titleTET-dependent regulation of retrotransposable elements in mouse embryonic stem cells.
dc.typeJournal Article
dc.rights.holder© 2016 The Author(s).
dc.identifier.doi10.1186/s13059-016-1096-8
dc.relation.isPartOfGenome Biol
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/27863519
pubs.issue1
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Blizard Institute - Research Students
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Genomics and Child Health
pubs.organisational-group/Queen Mary University of London/Faculty Reporting - Research Students
pubs.organisational-group/Queen Mary University of London/Faculty Reporting - Research Students/Faculty of Medicine & Dentistry PGRs
pubs.publication-statusPublished online
pubs.volume17


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