Abstract
Maintenance of genome stability requires control over the expression of transposable elements (TEs), whose activity can have substantial deleterious effects on the host. Chemical modification of DNA is a commonly used strategy to achieve this, and it has long been argued that the emergence of 5-methylcytosine (5mC) in many species was driven by the requirement to silence TEs. Potential roles in TE regulation have also been suggested for other DNA modifications, such as N6-methyladenine and oxidation derivatives of 5mC, although the underlying mechanistic relationships are poorly understood. Here, we discuss current evidence implicating DNA modifications and DNA-modifying enzymes in TE regulation across different species.
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Change history
20 March 2019
The originally published article contained an error in Figure 2a: for the left side of the figure part (showing piRNA-directed DNA methylation of mouse transposable elements), DNMT3A/B should have been DNMT3C. The article has now been corrected online.
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Acknowledgements
The authors thank M. Lorincz, R. Meehan and the reviewers for detailed comments on the manuscript, which led to extensive improvements to this Review. They also thank C. Feschotte for input on figure 1. They apologize to colleagues whose work was not cited owing to space limitations. M.R.B. is a Sir Henry Dale Fellow (101225/Z/13/Z), jointly funded by the Wellcome Trust and the Royal Society. Ö.D. has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement number 608765.
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Nature Reviews Genetics thanks J. Dejardin, M. Gauchier, J. Pontis, D. Trono and the other, anonymous reviewer(s) for their contribution to the peer review of this work.
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Glossary
- Genetic drift
-
The changes in the frequency of a given allele in a population due to random sampling. Genetic drift can lead to the fixation of a particular allelic variant in a population without any selective pressure.
- Horizontal propagation
-
Better known as horizontal gene transfer, horizontal propagation entails the transfer of genetic material between organisms. It contrasts with vertical transfer, which occurs from parents to offspring via the germline.
- PIWI-interacting RNAs
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(piRNAs). A class of small, single-stranded RNAs of 26–30 nucleotides that interacts with the PIWI family of proteins.
- Post-transcriptional gene silencing
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(PTGS). The process of silencing a gene after it has been transcribed, for example, by cleavage of its nascent RNA.
- Transcriptional gene silencing
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The silencing of a gene at the transcriptional level, that is, by preventing the transcriptional process, often by epigenetic modification of the locus to a less open conformation, disfavouring binding of RNA polymerase II.
- RNA-dependent DNA methylation
-
(RdDM). One of the key strategies for de novo and maintenance DNA methylation in Arabidopsis thaliana, whereby RNA molecules from expressed loci direct DNA methylation in a sequence-dependent manner.
- Pre-implantation development
-
The first phase of embryonic development that begins after fertilization and ends upon implantation of the blastocyst into the uterus.
- Endogenous small interfering RNAs
-
(endosiRNAs). Small RNAs (20–23 nucleotides) generated from double-stranded RNAs, including sense–antisense transcript hybrids.
- Primordial germ cells
-
(PGCs). The precursor cells of mammalian gametes that are specified at approximately embryonic day 6.25 in mice and that differentiate into oocytes or sperm.
- Naive pluripotency
-
A stem cell state that resembles that of the inner cell mass of the blastocyst.
- Chimeric transcripts
-
In the context of this Review, chimeric transcripts are RNA molecules that involve a fusion between a transposable element acting as a transcriptional promoter and a host gene.
- Clonal selection
-
In the context of cancer evolution, clonal selection entails the selective expansion of a particular cell due to genetic and/or epigenetic changes that confer a growth advantage.
- Zygotes
-
One-cell embryos resulting from the fusion of sperm with an oocyte, that is, fertilization.
- Orthologue
-
A gene from different species that has evolved from a common ancestor.
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Deniz, Ö., Frost, J.M. & Branco, M.R. Regulation of transposable elements by DNA modifications. Nat Rev Genet 20, 417–431 (2019). https://doi.org/10.1038/s41576-019-0106-6
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DOI: https://doi.org/10.1038/s41576-019-0106-6
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