Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sundaram, Vasavi, Cheng, Yong, Ma, Zhihai, Li, Daofeng, Xing, Xiaoyun, Edge, Peter, Snyder, Michael P., Wang, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
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
_version_ 1782346776948244480
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
work_keys_str_mv AT sundaramvasavi widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT chengyong widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT mazhihai widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT lidaofeng widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT xingxiaoyun widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT edgepeter widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT snydermichaelp widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks
AT wangting widespreadcontributionoftransposableelementstotheinnovationofgeneregulatorynetworks