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The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements

Although emerging evidence suggests that transposable elements (TEs) have contributed novel regulatory elements to the human genome, their global impact on transcriptional networks remains largely uncharacterized. Here we show that TEs have contributed to the human genome nearly half of its active e...

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Autores principales: Jacques, Pierre-Étienne, Jeyakani, Justin, Bourque, Guillaume
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649963/
https://www.ncbi.nlm.nih.gov/pubmed/23675311
http://dx.doi.org/10.1371/journal.pgen.1003504
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author Jacques, Pierre-Étienne
Jeyakani, Justin
Bourque, Guillaume
author_facet Jacques, Pierre-Étienne
Jeyakani, Justin
Bourque, Guillaume
author_sort Jacques, Pierre-Étienne
collection PubMed
description Although emerging evidence suggests that transposable elements (TEs) have contributed novel regulatory elements to the human genome, their global impact on transcriptional networks remains largely uncharacterized. Here we show that TEs have contributed to the human genome nearly half of its active elements. Using DNase I hypersensitivity data sets from ENCODE in normal, embryonic, and cancer cells, we found that 44% of open chromatin regions were in TEs and that this proportion reached 63% for primate-specific regions. We also showed that distinct subfamilies of endogenous retroviruses (ERVs) contributed significantly more accessible regions than expected by chance, with up to 80% of their instances in open chromatin. Based on these results, we further characterized 2,150 TE subfamily–transcription factor pairs that were bound in vivo or enriched for specific binding motifs, and observed that TEs contributing to open chromatin had higher levels of sequence conservation. We also showed that thousands of ERV–derived sequences were activated in a cell type–specific manner, especially in embryonic and cancer cells, and we demonstrated that this activity was associated with cell type–specific expression of neighboring genes. Taken together, these results demonstrate that TEs, and in particular ERVs, have contributed hundreds of thousands of novel regulatory elements to the primate lineage and reshaped the human transcriptional landscape.
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spelling pubmed-36499632013-05-14 The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements Jacques, Pierre-Étienne Jeyakani, Justin Bourque, Guillaume PLoS Genet Research Article Although emerging evidence suggests that transposable elements (TEs) have contributed novel regulatory elements to the human genome, their global impact on transcriptional networks remains largely uncharacterized. Here we show that TEs have contributed to the human genome nearly half of its active elements. Using DNase I hypersensitivity data sets from ENCODE in normal, embryonic, and cancer cells, we found that 44% of open chromatin regions were in TEs and that this proportion reached 63% for primate-specific regions. We also showed that distinct subfamilies of endogenous retroviruses (ERVs) contributed significantly more accessible regions than expected by chance, with up to 80% of their instances in open chromatin. Based on these results, we further characterized 2,150 TE subfamily–transcription factor pairs that were bound in vivo or enriched for specific binding motifs, and observed that TEs contributing to open chromatin had higher levels of sequence conservation. We also showed that thousands of ERV–derived sequences were activated in a cell type–specific manner, especially in embryonic and cancer cells, and we demonstrated that this activity was associated with cell type–specific expression of neighboring genes. Taken together, these results demonstrate that TEs, and in particular ERVs, have contributed hundreds of thousands of novel regulatory elements to the primate lineage and reshaped the human transcriptional landscape. Public Library of Science 2013-05-09 /pmc/articles/PMC3649963/ /pubmed/23675311 http://dx.doi.org/10.1371/journal.pgen.1003504 Text en © 2013 Jacques et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jacques, Pierre-Étienne
Jeyakani, Justin
Bourque, Guillaume
The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
title The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
title_full The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
title_fullStr The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
title_full_unstemmed The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
title_short The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
title_sort majority of primate-specific regulatory sequences are derived from transposable elements
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649963/
https://www.ncbi.nlm.nih.gov/pubmed/23675311
http://dx.doi.org/10.1371/journal.pgen.1003504
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