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TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells
BACKGROUND: 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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116139/ https://www.ncbi.nlm.nih.gov/pubmed/27863519 http://dx.doi.org/10.1186/s13059-016-1096-8 |
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author | de la Rica, Lorenzo Deniz, Özgen Cheng, Kevin C. L. Todd, Christopher D. Cruz, Cristina Houseley, Jonathan Branco, Miguel R. |
author_facet | de la Rica, Lorenzo Deniz, Özgen Cheng, Kevin C. L. Todd, Christopher D. Cruz, Cristina Houseley, Jonathan Branco, Miguel R. |
author_sort | de la Rica, Lorenzo |
collection | PubMed |
description | BACKGROUND: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1096-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5116139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-51161392016-11-25 TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells de la Rica, Lorenzo Deniz, Özgen Cheng, Kevin C. L. Todd, Christopher D. Cruz, Cristina Houseley, Jonathan Branco, Miguel R. Genome Biol Research BACKGROUND: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1096-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-18 /pmc/articles/PMC5116139/ /pubmed/27863519 http://dx.doi.org/10.1186/s13059-016-1096-8 Text en © The Author(s). 2016 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 de la Rica, Lorenzo Deniz, Özgen Cheng, Kevin C. L. Todd, Christopher D. Cruz, Cristina Houseley, Jonathan Branco, Miguel R. TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
title | TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
title_full | TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
title_fullStr | TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
title_full_unstemmed | TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
title_short | TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
title_sort | tet-dependent regulation of retrotransposable elements in mouse embryonic stem cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116139/ https://www.ncbi.nlm.nih.gov/pubmed/27863519 http://dx.doi.org/10.1186/s13059-016-1096-8 |
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