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Transposable elements and the epigenetic regulation of the genome

Key Points

  • Overlapping gene silencing mechanisms function to epigenetically repress transposable elements (TEs), including chromatin and DNA modification as well as RNAi.

  • TEs are a major component of constitutive heterochromatin at the centromere and telomere, and the regulation of these TEs is required for proper chromosome function.

  • TEs can function as the nucleation centers for facultative heterochromatin, as well as acting as boundaries to the spread of gene silencing.

  • Epialleles are formed due to the proximity of a gene to a TE, and the epigenetic regulation that the TE recruits.

  • TEs could have served as the building blocks for epigenetic phenomena such as X-chromosome inactivation, gene imprinting and V(D)J recombination.

  • The epigenetic control of transposable elements has had an important role in both organism and genome evolution.

  • How differing epigenetic control of TEs is established in genetically identical cells (variegation) remains a major question in understanding how TEs influence the genome.

Abstract

Overlapping epigenetic mechanisms have evolved in eukaryotic cells to silence the expression and mobility of transposable elements (TEs). Owing to their ability to recruit the silencing machinery, TEs have served as building blocks for epigenetic phenomena, both at the level of single genes and across larger chromosomal regions. Important progress has been made recently in understanding these silencing mechanisms. In addition, new insights have been gained into how this silencing has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome.

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Figure 1: Mechanisms of transposable element silencing.
Figure 2: The influence of transposable elements on gene expression.
Figure 3: The transposable element origins of V(D)J recombination.

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Acknowledgements

The authors apologize if relevant publications were not cited due to space constraints. R.K.S is supported by a postdoctoral fellowship from the US National Institutes of Health. Work in the authors' laboratory is supported by a grant from the National Institutes of Health to R.M.

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Glossary

Transposable elements

All mobile DNA segments in the genome, regardless of their mechanism of transposition.

Transpose

The movement of a genetic element from one location of the genome to another.

Autonomous element

A transposable element that produces all the proteins that are required for transposition.

Cryptic element

A transposable element that is epigenetically inactivated for a period of time and has lost the ability to mobilize.

Epigenetic

A heritable change that is not caused by a genetic mutation.

Non-autonomous element

A transposable element that does not produce the proteins required for transposition. These elements are dependent on the proteins produced by autonomous elements of the same element family to transpose.

Heterochromatin

The portion of interphase chromosomes that remains densely stained and condensed after cell division. Heterochromatic regions are generally gene poor, replicate late, and have a low level of transcription.

Imprinting

A gene is expressed from only one allele in a diploid organism, depending on the parent of origin.

Duplicative transposition

A mechanism of transposition that results in a copy of the element at both the excision and acceptor site. This can occur even after excision of the element by the process of gap repair.

Cut-and-paste transposition

A mechanism of transposition in which no copy of the element remains at the excision site.

Gap repair

A process whereby, after excision of a DNA transposon, the element can be copied back into the excision site from the template of the sister chromatid or homologous chromosome.

DNA transposon

Transposable elements that do not use a reverse-transcription step to integrate copies into the genome.

Terminal inverted repeat

Repeats that flank most DNA transposons and lie in an inverted orientation.

Retrotransposon

Transposable elements that use a reverse-transcription step to integrate copies into the genome. Also known as retroposons.

Presetting

Describes the inheritance of transposable-element

Position effect variegation

Unstable gene-expression patterns that are determined by the location of a gene.

LTR retrotransposon

Long terminal repeat retrotransposons are a type of retrotransposon that has repeats in a direct orientation at either end, in contrast with non-LTR retrotransposons.

Transposable element cycling

The transformation of a transposable element from an epigenetically inactive state to an active state, and back to an epigenetically inactive state, over the course of development or over multiple generations.

Polycomb group

A class of proteins, originally described in Drosophila melanogaster, the function of which is to maintain stable and heritable epigenetic repression.

non-LTR retrotransposon

A retrotransposon that is not flanked by long terminal repeats.

Constitutive heterochromatin

Heterochromatin that is heritable and is found at a particular locus at all times.

Facultative heterochromatin

Heterochromatin that switches to euchromatin at points during development.

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Slotkin, R., Martienssen, R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet 8, 272–285 (2007). https://doi.org/10.1038/nrg2072

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