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Review
. 2017 Jun;74(11):2055-2065.
doi: 10.1007/s00018-017-2454-8. Epub 2017 Feb 3.

Silencing of endogenous retroviruses by heterochromatin

Sophia Groh  1 , Gunnar Schotta  2
Affiliations
Review

Silencing of endogenous retroviruses by heterochromatin

Sophia Groh et al. Cell Mol Life Sci. 2017 Jun.

Abstract

Endogenous retroviruses (ERV) are an abundant class of repetitive elements in mammalian genomes. To ensure genomic stability, ERVs are largely transcriptionally silent. However, these elements also feature physiological roles in distinct developmental contexts, under which silencing needs to be partially relieved. ERV silencing is mediated through a heterochromatic structure, which is established by histone modification and DNA methylation machineries. This heterochromatic structure is largely refractory to transcriptional stimulation, however, challenges to the heterochromatic state, such as DNA replication, require re-establishment of the heterochromatic state in competition with transcriptional activators. In this review, we discuss the major pathways leading to efficient establishment of robust and inaccessible heterochromatin across ERVs.

Keywords: Atrx; Daxx; ERV restriction; H3K9me3; Retrotransposons; Setdb1; TEs; Transposable elements; Trim28.

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Figures

Fig. 1
Fig. 1
Heterochromatin establishment pathways act synergistically to re-establish heterochromatin upon challenges. The compact and less accessible state of heterochromatin can be compromised upon certain challenges, examples include replication, transcription through heterochromatin and DNA damage. The looser chromatin structure of challenged heterochromatin is more permissive to transcription factor binding. Competition between heterochromatin establishment pathways and transcription factor activity decides between re-establishment of heterochromatin or transcriptional activation of the ERV. If heterochromatin establishment pathways are compromised, e.g. upon Setdb1 or Dnmt1 knock-out, transcriptional activators dominate over heterochromatin re-establishment, leading to ERV derepression. MBD methyl DNA binding protein, TF transcription factor
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