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2017 ; 9
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): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation
of Long-Terminal Repeats (LTRs)
#MMPMID28561791
Hurst TP
; Magiorkinis G
Viruses
2017[May]; 9
(6
): ä PMID28561791
show ga
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.