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...

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Veröffentlicht in:Genome research Jg. 24; H. 12; S. 1963
Hauptverfasser: Sundaram, Vasavi, Cheng, Yong, Ma, Zhihai, Li, Daofeng, Xing, Xiaoyun, Edge, Peter, Snyder, Michael P, Wang, Ting
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.12.2014
Schlagworte:
Animals
Binding Sites
Cell Line
Chromatin - genetics
Chromatin - metabolism
Chromatin Immunoprecipitation
DNA Transposable Elements
Epigenomics
Evolution, Molecular
Gene Regulatory Networks
High-Throughput Nucleotide Sequencing
Humans
Mice
Multigene Family
Nucleotide Motifs
Organ Specificity - genetics
Position-Specific Scoring Matrices
Protein Binding
Transcription Factors - genetics
Transcription Factors - metabolism
ISSN:1549-5469, 1549-5469
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Zusammenfassung: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.
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content type line 23
ISSN:1549-5469
1549-5469
DOI:10.1101/gr.168872.113