Key Points
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Transposable elements (TEs) are increasingly recognized as a potent source of regulatory sequences in eukaryotic genomes
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The selfish replication cycle of TEs drove the evolution of finely tuned regulatory activities that favoured their propagation and has predisposed them to be co-opted for the regulation of host genes
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There is a growing number of examples of TE-derived sequences that have been co-opted to regulate important biological processes in organismal development and physiology
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Dysfunction of TE-derived regulatory sequences is also emerging as a potential driver of diseases including cancer and autoimmunity
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Functional genomics and genome-editing technologies herald an exciting era for understanding the biological effect of TEs
Abstract
Transposable elements (TEs) are a prolific source of tightly regulated, biochemically active non-coding elements, such as transcription factor-binding sites and non-coding RNAs. Many recent studies reinvigorate the idea that these elements are pervasively co-opted for the regulation of host genes. We argue that the inherent genetic properties of TEs and the conflicting relationships with their hosts facilitate their recruitment for regulatory functions in diverse genomes. We review recent findings supporting the long-standing hypothesis that the waves of TE invasions endured by organisms for eons have catalysed the evolution of gene-regulatory networks. We also discuss the challenges of dissecting and interpreting the phenotypic effect of regulatory activities encoded by TEs in health and disease.
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Acknowledgements
The authors apologize to many colleagues who have produced primary research on the topic but who could not be cited or discussed owing to space limitations. This work was supported by funds from the US National Institutes of Health (GM77582, GM112972, GM059290 to C.F. and GM114514 to N.C.E). E.B.C. was supported by a Howard Hughes Medical Institute postdoctoral fellowship from the Jane Coffin Childs Memorial Fund. N.C.E. was supported by the Biomedical Scholars Program of the Pew Charitable Trusts.
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FURTHER INFORMATION
Glossary
- Genetic drift
-
A process by which mutations become fixed in the population by chance alone.
- Cis-regulatory sequences
-
Segments of DNA that regulate the transcription of adjacent genes.
- Long terminal repeat elements
-
(LTR elements). A class of retrotransposons containing direct LTRs flanking the protein-coding sequence.
- Long interspersed nuclear elements
-
(LINEs). Class of non-long terminal repeat retrotransposons that retrotranspose by target-primed reverse transcription.
- Short interspersed nuclear elements
-
(SINEs). Class of non-autonomous retrotransposons that are copied by the LINE replication machinery.
- DNA transposons
-
Transposable elements that do not generate an RNA intermediate during transposition, which generally occurs through a 'cut-and-paste' mechanism.
- RNA sequencing
-
(RNA-seq). High-throughput sequencing of complementary DNAs derived from RNAs extracted from cells or tissues.
- Cap analysis of gene expression followed by sequencing
-
(CAGE-seq). A method used to precisely map the transcription start sites of capped RNAs genome-wide.
- Chromatin immunoprecipitation followed by sequencing
-
(ChIP-seq). A method for identifying protein–DNA interactions genome-wide. Following crosslinking, a protein of interest is immunoprecipitated and its binding sites in the genome are identified by high-throughput sequencing of the co-purified DNA fragments.
- Purifying selection
-
Selection against mutations that are deleterious to the fitness of the individual.
- Reporter assay
-
A putative cis-regulatory DNA sequence is cloned upstream of a reporter gene (such as luciferase) either in an episomal vector or as a chromosomally integrated construct and tested for its ability to enhance transcription of the reporter gene.
- Retrotransposon
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A type of transposable element that replicates through an RNA intermediate in a 'copy-and-paste' mechanism.
- Structural variation
-
Genomic variation resulting from large-scale DNA mutations such as deletions, insertions or rearrangements.
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Chuong, E., Elde, N. & Feschotte, C. Regulatory activities of transposable elements: from conflicts to benefits. Nat Rev Genet 18, 71–86 (2017). https://doi.org/10.1038/nrg.2016.139
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DOI: https://doi.org/10.1038/nrg.2016.139
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