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Widespread contribution of transposable elements to the innovation of gene regulatory networks
Transposable elements (TEs) have been shown to contain functional binding sites for certain transcription factors (TFs). However, the extent to which TEs contribute to the evolution of TF binding sites is not well known. We comprehensively mapped binding sites for 26 pairs of orthologous TFs in two...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248313/ https://www.ncbi.nlm.nih.gov/pubmed/25319995 http://dx.doi.org/10.1101/gr.168872.113 |
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author | Sundaram, Vasavi Cheng, Yong Ma, Zhihai Li, Daofeng Xing, Xiaoyun Edge, Peter Snyder, Michael P. Wang, Ting |
author_facet | Sundaram, Vasavi Cheng, Yong Ma, Zhihai Li, Daofeng Xing, Xiaoyun Edge, Peter Snyder, Michael P. Wang, Ting |
author_sort | Sundaram, Vasavi |
collection | PubMed |
description | Transposable elements (TEs) have been shown to contain functional binding sites for certain transcription factors (TFs). However, the extent to which TEs contribute to the evolution of TF binding sites is not well known. We comprehensively mapped binding sites for 26 pairs of orthologous TFs in two pairs of human and mouse cell lines (representing two cell lineages), along with epigenomic profiles, including DNA methylation and six histone modifications. Overall, we found that 20% of binding sites were embedded within TEs. This number varied across different TFs, ranging from 2% to 40%. We further identified 710 TF–TE relationships in which genomic copies of a TE subfamily contributed a significant number of binding peaks for a TF, and we found that LTR elements dominated these relationships in human. Importantly, TE-derived binding peaks were strongly associated with open and active chromatin signatures, including reduced DNA methylation and increased enhancer-associated histone marks. On average, 66% of TE-derived binding events were cell type-specific with a cell type-specific epigenetic landscape. Most of the binding sites contributed by TEs were species-specific, but we also identified binding sites conserved between human and mouse, the functional relevance of which was supported by a signature of purifying selection on DNA sequences of these TEs. Interestingly, several TFs had significantly expanded binding site landscapes only in one species, which were linked to species-specific gene functions, suggesting that TEs are an important driving force for regulatory innovation. Taken together, our data suggest that TEs have significantly and continuously shaped gene regulatory networks during mammalian evolution. |
format | Online Article Text |
id | pubmed-4248313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42483132015-06-01 Widespread contribution of transposable elements to the innovation of gene regulatory networks Sundaram, Vasavi Cheng, Yong Ma, Zhihai Li, Daofeng Xing, Xiaoyun Edge, Peter Snyder, Michael P. Wang, Ting Genome Res Research Transposable elements (TEs) have been shown to contain functional binding sites for certain transcription factors (TFs). However, the extent to which TEs contribute to the evolution of TF binding sites is not well known. We comprehensively mapped binding sites for 26 pairs of orthologous TFs in two pairs of human and mouse cell lines (representing two cell lineages), along with epigenomic profiles, including DNA methylation and six histone modifications. Overall, we found that 20% of binding sites were embedded within TEs. This number varied across different TFs, ranging from 2% to 40%. We further identified 710 TF–TE relationships in which genomic copies of a TE subfamily contributed a significant number of binding peaks for a TF, and we found that LTR elements dominated these relationships in human. Importantly, TE-derived binding peaks were strongly associated with open and active chromatin signatures, including reduced DNA methylation and increased enhancer-associated histone marks. On average, 66% of TE-derived binding events were cell type-specific with a cell type-specific epigenetic landscape. Most of the binding sites contributed by TEs were species-specific, but we also identified binding sites conserved between human and mouse, the functional relevance of which was supported by a signature of purifying selection on DNA sequences of these TEs. Interestingly, several TFs had significantly expanded binding site landscapes only in one species, which were linked to species-specific gene functions, suggesting that TEs are an important driving force for regulatory innovation. Taken together, our data suggest that TEs have significantly and continuously shaped gene regulatory networks during mammalian evolution. Cold Spring Harbor Laboratory Press 2014-12 /pmc/articles/PMC4248313/ /pubmed/25319995 http://dx.doi.org/10.1101/gr.168872.113 Text en © 2014 Sundaram et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Sundaram, Vasavi Cheng, Yong Ma, Zhihai Li, Daofeng Xing, Xiaoyun Edge, Peter Snyder, Michael P. Wang, Ting Widespread contribution of transposable elements to the innovation of gene regulatory networks |
title | Widespread contribution of transposable elements to the innovation of gene regulatory networks |
title_full | Widespread contribution of transposable elements to the innovation of gene regulatory networks |
title_fullStr | Widespread contribution of transposable elements to the innovation of gene regulatory networks |
title_full_unstemmed | Widespread contribution of transposable elements to the innovation of gene regulatory networks |
title_short | Widespread contribution of transposable elements to the innovation of gene regulatory networks |
title_sort | widespread contribution of transposable elements to the innovation of gene regulatory networks |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248313/ https://www.ncbi.nlm.nih.gov/pubmed/25319995 http://dx.doi.org/10.1101/gr.168872.113 |
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