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Viruses 2017, 9(6), 130; doi:10.3390/v9060130

Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)

1
Department of Zoology, University of Oxford, Oxford OX1 3PS, UK
2
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
*
Author to whom correspondence should be addressed.
Academic Editors: David J. Garfinkel and Katarzyna J. Purzycka
Received: 10 March 2017 / Revised: 22 May 2017 / Accepted: 22 May 2017 / Published: 31 May 2017
View Full-Text   |   Download PDF [241 KB, uploaded 23 June 2017]

Abstract

Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic activity and spread within the genome. For example, the LTRs are of critical importance as they contain promoter sequences and can regulate not only HERV expression but that of human genes. This is true even when the LTRs are located in intergenic regions or are in antisense orientation to the rest of the gene. Uncontrolled, this promoter activity could disrupt normal gene expression or transcript processing (e.g., splicing). Thus, control of HERVs and particularly their LTRs is essential for the cell to manage these elements and this control is achieved at multiple levels, including epigenetic regulations that permit HERV expression in the germline but silence it in most somatic tissues. We will discuss some of the common epigenetic mechanisms and how they affect HERV expression, providing detailed discussions of HERVs in stem cell, placenta and cancer biology. View Full-Text
Keywords: Endogenous retroviruses; HERVs; LTR; epigenetics; Krüppel-associated box zinc finger protein; KRAB-ZFP Endogenous retroviruses; HERVs; LTR; epigenetics; Krüppel-associated box zinc finger protein; KRAB-ZFP
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hurst, T.P.; Magiorkinis, G. Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs). Viruses 2017, 9, 130.

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