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.
Highlights
Retroviruses integrate a reverse transcribed double stranded DNA copy of their viral genome into the chromosomal DNA of cells they infect
The complete sequencing of the human genome produced an unexpected windfall—the discovery that genetic elements associated with endogenous retroviruses (ERVs) far outnumbered protein-encoding genes
Among human ERVs (HERVs) that retain some degree of function, several have acquired physiologically relevant roles in their hosts
Summary
ERV-9 LTRs are found only in the primate genome where they have been maintained for at least 15 million years [6]. One feature that distinguishes ERV-9 LTRs from other endogenous human LTRs is the presences of 14 tandem repeat elements that contain recurrent CCAAT, GTGGGGA and GATA nucleotide motifs. These DNA motifs bind transcription factors that are expressed preferentially in hematopoietic progenitor cells [7] and in reproductive tissues [8,9,10,11]. Using a globin ERV-9 specific sequence probe for in situ hybridization analysis, ERV-9 initiated gene expression in transgenic zebrafish and in humans occurs in both oocytes and various progenitor cells but not testes [13]. ERV-9 promoter activity in oocytes has not been determined
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