Genomic Distribution and Transcription of Solitary HERV-K LTRs

Leib-Mösch, Christine; Haltmeier, Manuela; Werner, Thomas; Geigl, Eva-María; Brack‐Werner, Ruth; Francke, Uta; Erfle, Volker; Hehlmann, Rüdiger

doi:10.1006/geno.1993.1464

Cited by 112 publications

(87 citation statements)

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“…While there are only about 30 -50 full-length HERV-K sequences in the human genome, there are an estimated 10 000 solitary long terminal repeats (LTRs) from HERV-K (Leib- Mosch et al, 1993). At least some of the solitary LTRs can drive reporter gene expression as determined from an HERV-K LTRcontaining transgene (Casau et al, 1999).…”

Section: Hypomethylation Of Moderately Repeated Dna Sequences In Cancermentioning

confidence: 99%

DNA methylation in cancer: too much, but also too little

2002

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Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but these two types of epigenetic abnormalities usually seem to affect different DNA sequences. Much more of the genome is generally subject to undermethylation rather than overmethylation. Genomic hypermethylation in cancer has been observed most often in CpG islands in gene regions. In contrast, very frequent hypomethylation is seen in both highly and moderately repeated DNA sequences in cancer, including heterochromatic DNA repeats, dispersed retrotransposons, and endogenous retroviral elements. Also, unique sequences, including transcription control sequences, are often subject to cancer-associated undermethylation. The high frequency of cancer-linked DNA hypomethylation, the nature of the affected sequences, and the absence of associations with DNA hypermethylation are consistent with an independent role for DNA undermethylation in cancer formation or tumor progression. Increased karyotypic instability and activation of tumor-promoting genes by cis or trans effects, that might include altered heterochromatin-euchromatin interactions, may be important consequences of DNA hypomethylation which favor oncogenesis. The relationship of DNA hypomethylation to tumorigenesis is important to be considered in the light of cancer therapies involving decreasing DNA methylation. Inducing DNA hypomethylation may have short-term anticancer effects, but might also help speed tumor progression from cancer cells surviving the DNA demethylation chemotherapy.

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Section: Hypomethylation Of Moderately Repeated Dna Sequences In Cancermentioning

confidence: 99%

DNA methylation in cancer: too much, but also too little

2002

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“…Because of their relatively long residence in the genome, the majority of HERV elements are riddled with deleterious mutations, large deletions, and insertions of other repetitive elements. In addition, the exogenous viral counterparts of HERVs have most likely been extinct for many millions of years, but it is clear that these elements have expanded in copy number significantly throughout the course of primate evolution, perhaps through intracellular retrotransposition mechanisms (Leib-Mosch et al 1993;Goodman et al 1998;Costas and Naveira 2000) as well as replication as viruses and reinfection (Belshaw et al 2004). The HERV-K family in particular has been actively expanding in our genome throughout the last 5-20 million years, during the period of radiation of hominids (Medstrand and Mager 1998;Barbulescu et al 1999;Coffin 2001, 2004).…”

Section: Ndogenous Retroviruses Arise From Retroviralmentioning

confidence: 99%

Human Endogenous Retroviral Elements as Indicators of Ectopic Recombination Events in the Primate Genome

Hughes

Coffin

2005

Genetics

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HERV elements make up a significant fraction of the human genome and, as interspersed repetitive elements, have the capacity to provide substrates for ectopic recombination and gene conversion events. To understand the extent to which these events occur and gain further insight into the complex evolutionary history of these elements in our genome, we undertook a phylogenetic study of the long terminal repeat sequences of 15 HERV-K(HML-2) elements in various primate species. This family of human endogenous retroviruses first entered the primate genome between 35 and 45 million years ago. Throughout primate evolution, these elements have undergone bursts of amplification. From this analysis, which is the largestscale study of HERV sequence dynamics during primate evolution to date, we were able to detect intraelement gene conversion and recombination at five HERV-K loci. We also found evidence for replacement of an ancient element by another HERV-K provirus, apparently reflecting an occurrence of retroviral integration by homologous recombination. The high frequency of these events casts doubt on the accuracy of integration time estimates based only on divergence between retroelement LTRs.

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“…In addition, about 10,000 solitary LTRs are scattered throughout the human genome (16). HTDV/ HERV-K related sequences can be traced back to the time of divergence of Old and New World monkeys (15,32,33).…”

Section: Htdv/herv-k a Family Coding For Viral Particlesmentioning

confidence: 99%