Transposable elements generate regulatory novelty in a tissue-specific fashion
File(s)33_Trizzino_et_al_2018_BMC_GENOMICS.pdf (2.62 MB)
Published version
Author(s)
Trizzino, Marco
Kapusta, Aurélie
Brown, Christopher D
Type
Journal Article
Abstract
Background
Transposable elements (TE) are an important source of evolutionary novelty in gene regulation. However, the mechanisms by which TEs contribute to gene expression are largely uncharacterized.
Results
Here, we leverage Roadmap and GTEx data to investigate the association of TEs with active and repressed chromatin in 24 tissues. We find 112 human TE families enriched in active regions of the genome across tissues. Short Interspersed Nuclear Elements (SINEs) and DNA transposons are the most frequently enriched classes, while Long Terminal Repeat Retrotransposons (LTRs) are often enriched in a tissue-specific manner. We report across-tissue variability in TE enrichment in active regions. Genes with consistent expression across tissues are less likely to be associated with TE insertions. TE presence in repressed regions similarly follows tissue-specific patterns. Moreover, different TE classes correlate with different repressive marks: LTRs and Long Interspersed Nuclear Elements (LINEs) are overrepresented in regions marked by H3K9me3, while the other TEs are more likely to overlap regions with H3K27me3. Young TEs are typically enriched in repressed regions and depleted in active regions. We detect multiple instances of TEs that are enriched in tissue-specific active regulatory regions. Such TEs contain binding sites for transcription factors that are master regulators for the given tissue. These TEs are enriched in intronic enhancers, and their tissue-specific enrichment correlates with tissue-specific variations in the expression of the nearest genes.
Conclusions
We provide an integrated overview of the contribution of TEs to human gene regulation. Expanding previous analyses, we demonstrate that TEs can potentially contribute to the turnover of regulatory sequences in a tissue-specific fashion.
Transposable elements (TE) are an important source of evolutionary novelty in gene regulation. However, the mechanisms by which TEs contribute to gene expression are largely uncharacterized.
Results
Here, we leverage Roadmap and GTEx data to investigate the association of TEs with active and repressed chromatin in 24 tissues. We find 112 human TE families enriched in active regions of the genome across tissues. Short Interspersed Nuclear Elements (SINEs) and DNA transposons are the most frequently enriched classes, while Long Terminal Repeat Retrotransposons (LTRs) are often enriched in a tissue-specific manner. We report across-tissue variability in TE enrichment in active regions. Genes with consistent expression across tissues are less likely to be associated with TE insertions. TE presence in repressed regions similarly follows tissue-specific patterns. Moreover, different TE classes correlate with different repressive marks: LTRs and Long Interspersed Nuclear Elements (LINEs) are overrepresented in regions marked by H3K9me3, while the other TEs are more likely to overlap regions with H3K27me3. Young TEs are typically enriched in repressed regions and depleted in active regions. We detect multiple instances of TEs that are enriched in tissue-specific active regulatory regions. Such TEs contain binding sites for transcription factors that are master regulators for the given tissue. These TEs are enriched in intronic enhancers, and their tissue-specific enrichment correlates with tissue-specific variations in the expression of the nearest genes.
Conclusions
We provide an integrated overview of the contribution of TEs to human gene regulation. Expanding previous analyses, we demonstrate that TEs can potentially contribute to the turnover of regulatory sequences in a tissue-specific fashion.
Date Issued
2018-06-18
Date Acceptance
2018-06-01
Citation
BMC Genomics, 2018, 19
ISSN
1471-2164
Publisher
BMC
Journal / Book Title
BMC Genomics
Volume
19
Copyright Statement
© The Author(s). 2018 Open Access This 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.
License URL
Identifier
http://dx.doi.org/10.1186/s12864-018-4850-3
Publication Status
Published
Article Number
468
Date Publish Online
2018-06-18