Tissue specificity of enhancer and promoter activities of a HERV-K(HML-2) LTR

Ruda, Vera M.; Akopov, S. B.; Trubetskoy, D.O; Manuylov, Nikolay L.; Ветчинова, А. С.; Zavalova, L. L.; Николаев, Л. Г.; Свердлов, Е. Д.

doi:10.1016/j.virusres.2004.02.036

Cited by 64 publications

(58 citation statements)

References 31 publications

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“…It is therefore likely that the Accord LTR intrinsically carries the regulatory sequences to confer the tissue-specific expression. Other TEs have also been shown to carry tissue-specific enhancers in their LTR or 59-UTR (Pi et al 2004;Ruda et al 2004). Enhancer sequences are presumably involved in the expression of TEs in temporal and tissue-specific patterns as shown by the BDGP embryonic in situ hybridization project (Tomancak et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Cis-Regulatory Elements in the Accord Retrotransposon Result in Tissue-Specific Expression of the Drosophila melanogaster Insecticide Resistance Gene Cyp6g1

et al. 2007

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Transposable elements are a major mutation source and powerful agents of adaptive change. Some transposable element insertions in genomes increase to a high frequency because of the selective advantage the mutant phenotype provides. Cyp6g1-mediated insecticide resistance in Drosophila melanogaster is due to the upregulation of the cytochrome P450 gene Cyp6g1, leading to the resistance to a variety of insecticide classes. The upregulation of Cyp6g1 is correlated with the presence of the long terminal repeat (LTR) of an Accord retrotransposon inserted 291bp upstream of the Cyp6g1 transcription start site. This resistant allele (DDT-R) is currently at a high frequency in D. melanogaster populations around the world. Here, we characterize the spatial expression of Cyp6g1 in insecticide-resistant and -susceptible strains. We show that the Accord LTR insertion is indeed the resistance-associated mutation and demonstrate that the Accord LTR carries regulatory sequences that increase the expression of Cyp6g1 in tissues important for detoxification, the midgut, Malpighian tubules, and the fat body. This study provides a significant example of how changes in tissue-specific gene expression caused by transposableelement insertions can contribute to adaptation.

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Section: Discussionmentioning

confidence: 99%

Cis-Regulatory Elements in the Accord Retrotransposon Result in Tissue-Specific Expression of the Drosophila melanogaster Insecticide Resistance Gene Cyp6g1

et al. 2007

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“…Further, the youngest 11 HK2 are polymorphic in the human population (3,9,12). As HK2 is the most recent retrovirus to enter the genome, it is not surprising that HK2 still is transcriptionally active (13)(14)(15)(16)(17)(18)(19). The expression of HK2 viral RNA, proteins, and virus-like particles (VLPs) is detectable in breast cancer, leukemia, melanoma, and teratocarcinoma cell lines.…”

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confidence: 99%

Human Endogenous Retrovirus Type K (HERV-K) Particles Package and Transmit HERV-K–Related Sequences

Contreras-Galindo

Kaplan

Dube

et al. 2015

J Virol

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Human endogenous retroviruses (HERV) make up 8% of the human genome. While the youngest of these retroviruses, HERV-K(HML-2), termed HK2, is able to code for all viral proteins and produce virus-like particles, it is not known if these virus particles package and transmit HK2-related sequences. Here, we analyzed the capacity of HK2 for packaging and transmitting HK2 sequences. We created an HK2 probe, termed Bogota, which can be packaged into HK2 viruses, and transfected it into cells that make HK2 particles. Supernatants of the transfected cells, which contained HK2 viral particles, then were added to target cells, and the transmissibility of the HK2 Bogota reporter was tracked by G418 resistance. Our studies revealed that contemporary HK2 virions produced by some teratocarcinoma and breast cancer cell lines, as well as by peripheral blood lymphocytes from lymphoma patients, can package HK2 Bogota probes, and these viruses transmitted these probes to other cells. After transmission, HK2 Bogota transcripts undergo reverse transcription, a step impaired by antiretroviral agents or by introduction of mutations into the probe sequences required for reverse transcription. HK2 viruses were more efficiently transmitted in the presence of HK2 Rec or HIV-1 Tat and Vif. Transmitted Bogota probes formed episomes but did not integrate into the cellular genome. Resistance to integration might explain the relatively low number of HK2 insertions that were acquired during the last 25 million years of evolution. Whether transient transmission of modern HK2 sequences, which encode two putative oncoproteins, can lead to disease remains to be studied. IMPORTANCERetroviruses invaded the genome of human ancestors over the course of millions of years, yet these viruses generally have been inactivated during evolution, with only remnants of these infectious sequences remaining in the human genome. One of these viruses, termed HK2, still is capable of producing virus particles, although these particles have been regarded as being noninfectious. Using a genetic probe derived from HK2, we have discovered that HK2 viruses produced in modern humans can package HK2 sequences and transmit them to various other cells. Furthermore, the genetic sequences packaged in HK2 undergo reverse transcription. The transmitted probe circularized in the cell and failed to integrate into the cellular genome. These findings suggest that modern HK2 viruses can package viral RNA and transmit it to other cells. Contrary to previous views, we provide evidence of an extracellular viral phase of modern HK2 viruses. We have no evidence of sustained, spreading infection.A ctively replicating retroviruses infected the germ line multiple times over the millions of years of human evolution. These sequences were transmitted vertically in a Mendelian fashion to the next generation; therefore, they became a stable part of the inherited genetic material. Relics of these retroviral infections presently make up approximately 8% of the modern human genome. These retro...

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“…In the human genome, most human endogenous retroviruses (HERVs) are present as solitary long terminal repeat (LTR) structures, which are formed Edited by Hidenori Nishiharathrough HR events between LTRs of full-length HERVs (Hughes and Coffin, 2004;Mayer et al, 2005;Lee et al, 2009b). Human-specific LTRs are involved in the specific activation of functional genes, polyadenylation signals, splice sites, and as antisense regulators in embryonic and cancer tissues (Schulte et al, 2000;Kim et al, 2005;Ruda et al, 2004;Sin et al, 2006;Illarionova et al, 2007;Huh et al, 2008;Ahn et al, 2009). Retroelements may also function through HR and nonhomologous end joining (NHEJ) (Hughes and Coffin, 2001).…”

Section: Genomic Instability Induced By Retroelementsmentioning

confidence: 99%

Retroelements: molecular features and implications for disease

et al. 2013

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Eukaryotic genomes comprise numerous retroelements that have a major impact on the structure and regulation of gene function. Retroelements are regulated by epigenetic controls, and they generate multiple miRNAs that are involved in the induction and progression of genomic instability. Elucidation of the biological roles of retroelements deserves continuous investigation to better understand their evolutionary features and implications for disease.

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Tissue specificity of enhancer and promoter activities of a HERV-K(HML-2) LTR

Cited by 64 publications

References 31 publications

Cis-Regulatory Elements in the Accord Retrotransposon Result in Tissue-Specific Expression of the Drosophila melanogaster Insecticide Resistance Gene Cyp6g1

Cis-Regulatory Elements in the Accord Retrotransposon Result in Tissue-Specific Expression of the Drosophila melanogaster Insecticide Resistance Gene Cyp6g1

Human Endogenous Retrovirus Type K (HERV-K) Particles Package and Transmit HERV-K–Related Sequences

Retroelements: molecular features and implications for disease

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