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Strain-Specific Epigenetic Regulation of Endogenous Retroviruses: The Role of Trans-Acting Modifiers.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Elmer, Jessica L 
Ferguson-Smith, Anne C 

Abstract

Approximately 10 percent of the mouse genome consists of endogenous retroviruses (ERVs), relics of ancient retroviral infections that are classified based on their relatedness to exogenous retroviral genera. Because of the ability of ERVs to retrotranspose, as well as their cis-acting regulatory potential due to functional elements located within the elements, mammalian ERVs are generally subject to epigenetic silencing by DNA methylation and repressive histone modifications. The mobilisation and expansion of ERV elements is strain-specific, leading to ERVs being highly polymorphic between inbred mouse strains, hinting at the possibility of the strain-specific regulation of ERVs. In this review, we describe the existing evidence of mouse strain-specific epigenetic control of ERVs and discuss the implications of differential ERV regulation on epigenetic inheritance models. We consider Krüppel-associated box domain (KRAB) zinc finger proteins as likely candidates for strain-specific ERV modifiers, drawing on insights gained from the study of the strain-specific behaviour of transgenes. We conclude by considering the coevolution of KRAB zinc finger proteins and actively transposing ERV elements, and highlight the importance of cross-strain studies in elucidating the mechanisms and consequences of strain-specific ERV regulation.

Description

Keywords

ERVs, KRAB zinc finger proteins, epigenetic regulation, metastable epialleles, modifiers, strain-specific, transgenes, Animals, Endogenous Retroviruses, Epigenesis, Genetic, Gene Expression Regulation, Humans, Kruppel-Like Transcription Factors, Mice, Mice, Inbred Strains, Promoter Regions, Genetic, Retroviridae Infections, Trans-Activators

Journal Title

Viruses

Conference Name

Journal ISSN

1999-4915
1999-4915

Volume Title

12

Publisher

MDPI AG

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/R009791/1)
Wellcome Trust (210757/Z/18/Z)
Biotechnology and Biological Sciences Research Council (BB/R009996/1)
Biotechnology and Biological Sciences Research Council (1795629)