CpG Methylation Directly Regulates Transcriptional Activity of the Human Endogenous Retrovirus Family HERV-K(HML-2)

Lavie, Laurence; Kitova, Milena; Maldener, Esther; Meese, Eckart; Mayer, Jens

doi:10.1128/jvi.79.2.876-883.2005

Cited by 194 publications

(167 citation statements)

References 44 publications

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“…Exogenous retroviral DNAs can be inactivated due to de novo DNA methylation and were able to integrate into human genome to become part of it [34]. Indeed, human genome contains DNA sequences resembling the retroviral long terminal repeats (LTRs) [35] and the transposable elements. Interestingly, viruses can find ways to counteract this cellbased modification and even take advantages of it.…”

Section: Virus Infection Epigenetics Alter-ations and Carcinogenesismentioning

confidence: 99%

Epigenetic changes in virus-associated human cancers

Leu

Chang

2005

Cell Res

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Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding of specific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is a prevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increased activity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players in regulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing and the signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus 40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection of epigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigenetic changes should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection, prognosis, and therapy of cancer.

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Section: Virus Infection Epigenetics Alter-ations and Carcinogenesismentioning

confidence: 99%

Epigenetic changes in virus-associated human cancers

Leu

Chang

2005

Cell Res

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“…By introducing potentially active promoters throughout the genome, TEs may increase the overall level of transcription-related stress, inflating the average number of DSBs per cell cycle. This phenomenon is no doubt largely mitigated in normal cells due to the repression of many TE promoters by methylation and associated chromatin structures [59][60][61]. However, some TE promoters evidently do manage-if only temporarily-to escape these repression mechanisms as evidenced by their continued survival in the vast majority of taxa surveyed.…”

Section: Transcription and Recombination-increased Transcriptional Acmentioning

confidence: 99%

“…These epigenetic alterations can be considered physical alterations in the genome's information repository. Because of their potential to disrupt normal biological function during proliferation, a number of mammalian taxa have employed epigenetic modifications, many of which serve to constrain TE activity [60,[83][84][85][86]. As a consequence, the insertion of TEs at particular regions of the genome can result in the recruitment of chromatin modulating factors, typically via CpG methylation and subsequent histone deacetylation, to the region containing the inserted element.…”

Section: Tes Alter Epigenetic Regulatorymentioning

confidence: 99%

Inviting instability: Transposable elements, double-strand breaks, and the maintenance of genome integrity

Hedges

Deininger

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

279

248

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The ubiquity of mobile elements in mammalian genomes poses considerable challenges for the maintenance of genome integrity. The predisposition of mobile elements towards participation in genomic rearrangements is largely a consequence of their interspersed homologous nature. As tracts of nonallelic sequence homology, they have the potential to interact in a disruptive manner during both meiotic recombination and DNA repair processes, resulting in genomic alterations ranging from deletions and duplications to large-scale chromosomal rearrangements. Although the deleterious effects of transposable element (TE) insertion events have been extensively documented, it is arguably through post-insertion genomic instability that they pose the greatest hazard to their host genomes. Despite the periodic generation of important evolutionary innovations, genomic alterations involving TE sequences are far more frequently neutral or deleterious in nature. The potentially negative consequences of this instability are perhaps best illustrated by the 25 human genetic diseases that are attributable to TE-mediated rearrangements. Some of these rearrangements, such as those involving the MLL locus in leukemia and the LDL receptor in familial hypercholesterolemia, represent recurrent mutations that have independently arisen multiple times in human populations. While TE-instability has been a potent force in shaping eukaryotic genomes and a significant source of genetic disease, much concerning the mechanisms governing the frequency and variety of these events remains to be clarified. Here we survey the current state of knowledge regarding the mechanisms underlying mobile element-based genetic instability in mammals. Compared to simpler eukaryotic systems, mammalian cells appear to have several modifications to their DNA-repair ensemble that allow them to better cope with the large amount of interspersed homology that has been generated by TEs. In addition to the disruptive potential of nonallelic sequence homology, we also consider recent evidence suggesting that the endonuclease products of TEs may also play a key role in instigating mammalian genomic instability.

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“…Une levée de cette répression épigénétique par les herpèsvirus pourrait ainsi expliquer la réactivation de certains HERV [8]. Comme représenté dans la Figure 1, HCMV et EBV présentent un potentiel « déméthylant » des séquences HERV [9,10].…”

Section: Rôle De Hcmv Et Ebv Sur La Méthylationunclassified