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. 2011 Jun;3(6):901-5.
doi: 10.3390/v3060901. Epub 2011 Jun 21.

Role of human endogenous retroviral long terminal repeats (LTRs) in maintaining the integrity of the human germ line

Meihong Liu  1 , Maribeth V Eiden
Affiliations

Role of human endogenous retroviral long terminal repeats (LTRs) in maintaining the integrity of the human germ line

Meihong Liu et al. Viruses. 2011 Jun.

Abstract

Retroviruses integrate a reverse transcribed double stranded DNA copy of their viral genome into the chromosomal DNA of cells they infect. Occasionally, exogenous retroviruses infect germ cells and when this happens a profound shift in the virus host dynamic occurs. Retroviruses maintained as hereditable viral genetic material are referred to as endogenous retroviruses (ERVs). After millions of years of co-evolution with their hosts many human ERVs retain some degree of function and a few have even become symbionts. Thousands of copies of endogenous retrovirus long terminal repeats (LTRs) exist in the human genome. There are approximately 3000 to 4000 copies of the ERV-9 LTRs in the human genome and like other solo LTRs, ERV-9 LTRs can exhibit distinct promoter/enhancer activity in different cell lineages. It has been recently reported that a novel transcript of p63, a primordial member of the p53 family, is under the transcriptional control of an ERV-9 LTR [1]. The expression of different p63 transcript isoforms has been previously shown to have an important role in replenishing cutaneous epithelial stem cells and maintaining the fidelity of the female germ line [2]. In this recent report, a novel p63 transcript, designated GTAp63, is described as specifically expressed in healthy human testes and germ cell precursors of human testes but not in testicular cancer cells. The ability of ERV-9 regulatory regions to contribute to the maintenance of male germ line stability is yet another example of how ERVs have evolved to serve an important function in the physiology of their human hosts.

Keywords: genomic stability; primate evolution; retroelement.

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Figures

Figure 1.
Figure 1.
Genomic organization of human p63 locus. The p63 locus contains more than one promoter. Arrows designate the transcription initiation sites for the TAp63 (TA) and ΔNp63 (ΔN) as well as GTAp63 (GTA) transcripts from its distinct ERV-9 promoter. Alternate splicing within the 3′ region of the gene results in the formation of the α, β and γ isoforms of the TAp63 and ΔNp63. The main structural domains include the N-terminal transactivation domain (TA), specific to the TAp63α and GTApTAp63α isoforms, DNA binding (green), oligomerization (yellow), SAM, or sterile alpha motif, a protein-protein interaction domain (purple) and the TID transactivation inhibitory domain (orange) [16]. The promoter located within the U3 of an ERV-9 LTR initiates transcription of GTAp63. The coding region corresponding to the 19 residues in the GTAp63 protein derived from the ERV-9 U5 is shown in pink.
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