Activation of intracistemal a particles by 5-azacytidine in mouse Ki-BALB cell line

Lasneret, J; Canivet, M; De, Fan; Tobaly, J.; Emanoil-Ravicovitch, R; Périès, J.

doi:10.1016/0042-6822(83)90275-1

Cited by 20 publications

(13 citation statements)

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“…Similarly, treatment with 5-AZC induced Epstein-Barr virus early antigens in latently infected human lymphoid cells (Ben-Sasson et al, 1981). Furthermore, an increase in hepatitis B virus core transcripts (Korba et al, 1985) as well as expression of retrovirus type C and type A sequences (Hsiao et al, 1986;Lasneret et al, 1983) and genomes (Jaenisch et al, 1985) have been demonstrated after 5-AZC treatment. We therefore hypothesized that methylation of the HSV genome might be involved in the induction 0000-8084 © 1988 SGM Short communication or maintenance of the latent state by down-regulating viral gene expression and that druginduced hypomethylation might, therefore, enhance reactivation of latent HSV-2.…”

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confidence: 89%

Enhanced in vitro Reactivation of Herpes Simplex Virus Type 2 from Latently Infected Guinea-pig Neural Tissues by 5-Azacytidine

Stephanopoulos

Kappes

Bernstein

1988

Journal of General Virology

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SUMMARY5-Azacytidine (5-AZC) reduces cytosine methylation in DNA and has been reported to activate quiescent virus genes. Treatment of explant cultures of latently herpes simplex virus type 2 (HSV-2)-infected guinea-pig dorsal root ganglia and spinal cords in vitro with 5-AZC significantly enhanced the rate of HSV recovery. Both the number of isolates from ganglia (P < 0.001) and the rate of recovery (P < 0.001) were significantly increased with the addition of 50 ~tM-5-AZC to explant cultures. Increased virus recovery appeared to be due to the induction of reactivation of latent virus, rather than an increase in replication, since 5-AZC inhibited HSV replication. These data support a role for methylation in HSV latency and reactivation.

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confidence: 89%

Enhanced in vitro Reactivation of Herpes Simplex Virus Type 2 from Latently Infected Guinea-pig Neural Tissues by 5-Azacytidine

Stephanopoulos

Kappes

Bernstein

1988

Journal of General Virology

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“…In vitro methylation of the IAP LTR inhibits its promoter activity [22]. Treating murine cells with the (DNA) hypomethylating agent 5-azacytidine releases the repression of endogenous IAP elements [23]. Furthermore, deletion of the maintenance DNA methyltransferase enzyme Dnmt1 causes a dramatic (50-100-fold) upregulation of IAP elements in early mouse embryos [24].…”

Section: Epigenetic Regulation Patterns Of Iaps Differ Among Tissuesmentioning

confidence: 99%

Is there a role for endogenous retroviruses to mediate long-term adaptive phenotypic response upon environmental inputs?

Sharif

Shinkai

Koseki

2013

Phil. Trans. R. Soc. B

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Endogenous retroviruses (ERVs) are long terminal repeat-containing virus-like elements that have colonized approximately 10 per cent of the present day mammalian genomes. The intracisternal A particles (IAPs) are a class of ERVs that is currently highly active in the rodents. IAP elements can influence the transcription profile of nearby genes by providing functional promoter elements and modulating local epigenetic landscape through changes in DNA methylation and histone (H3K9) modifications. Despite the potential role for IAPs in gene regulation, the precise genomic locations where these elements are integrated are not well understood. To address this issue, we have identified more than 400 novel IAP insertion sites within/near annotated genes by searching the murine genome, which suggests that the impact of IAP elements on local and/or global gene regulation could be more profound than was previously expected. On the basis of our independent analyses and already published reports, here we argue that IAPs and ERV elements in general could have an evolutionary role for modulating phenotypic plasticity upon environmental inputs, and that this could be mediated through specific stages of embryonic development such as placentation during which the epigenetic constraints on IAP elements are partially relaxed.

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“…DNA methylation has been implicated in the regulation of intracisternal A-particle (IAP) gene expression. Expression of IAP proviral elements in various normal and transformed mouse cells is inversely correlated with their methylation state (22,29,34) and specifically with the methylation state of their 5' long terminal repeats (LTRs) (15,35). In vitro CpG methylation at HhaI or HpaII sites in the 5' LTR of the mouse proviral IAP clone MIA14 resulted in a marked decrease in promoter activity, as measured by transient expression assays with a chloramphenicol acetyltransferase (CAT) reporter gene in COS7 cells (15) or 293 cells (13).…”

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confidence: 99%

Binding of the transcription factor EBP-80 mediates the methylation response of an intracisternal A-particle long terminal repeat promoter.

Falzon

Kuff

1991

Mol. Cell. Biol.

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Intracisternal A-particle (IAP) expression in mouse cells has been correlated with hypomethylation of HhaI and Hpal sites in proviral long terminal repeats (LTRs). In a previous study, in vitro methylation of three HhaI sites in the U3 region of the LTR from the cloned genomic LAP element, MIA14, was shown to inhibit promoter activity in vivo. In this study, we found by site-directed mutagenesis that the two more downstream HhaI sites within this LTR were responsible for the methylation effects on promoter activity in vivo; methylation of the other (5') HhaI site, which lies within a putative SP1 binding domain, did not affect promoter activity. Methylation of the HhaI sites also inhibited promoter activity of the LTR in a cell-free transcription system. Exonuclease Im footprinting demonstrated methylation-induced changes in protein binding over the region encompassing the downstream HhaI site, designated the Enh2 domain. The protein that interacts specifically with this domain, EBP-80, was characterized in a previous study (M. Falzon and E. L. Kuff, J. Biol. Chem. 264:21915-21922, 1989). We show here that the presence of methylcytosine in the HhaI site within the Enh2 domain inhibited binding of EBP-80 in vitro. The methylated MIA14 LTR construct was much less responsive to added EBP-80 in an in vitro transcription system than was the unmethylated construct. These data suggest that CpG methylation within the Enh2 domain may exert its effect on transcription in vivo by altering the interaction between EBP-80 and its cognate DNA sequence.Site-specific promoter methylation causes gene inactivation in a number of viral and nonviral eucaryotic systems (for reviews, see references 10, 11, and 36). For example, in vitro methylation at specific sites interferes with expression of the a-globin gene (7, 37), the herpes simplex thymidine kinase gene (5), and the adenine phosphoribosyltransferase gene (26). DNA methylation has been implicated in the regulation of intracisternal A-particle (IAP) gene expression. Expression of IAP proviral elements in various normal and transformed mouse cells is inversely correlated with their methylation state (22,29,34) (Fig. 1). We show here by site-directed mutagenesis studies that only two of these sites (sites b and c; Fig. 1) are involved in the methylation effect.Methylation may influence LTR function by altering the interaction between one or more regulatory proteins and their binding sites. In this study, we show that the exonuclease III footprint of the HhaI-methylated LTR in the presence of crude nuclear extract is perturbed over one of the methylation sites (site c; Fig. 1). We also show that a purified DNA-binding protein (EBP-80) specific for the LTR region containing this site fails to bind to an oligonucleotide containing the methylated form of the HhaI site c. The MIA14 LTR methylated at the HhaI site c is a less effective * Corresponding author.promoter of transcription in vitro than is its unmethylated counterpart and responds poorly to added EBP-80. These results provid...

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Activation of intracistemal a particles by 5-azacytidine in mouse Ki-BALB cell line

Cited by 20 publications

References 10 publications

Enhanced in vitro Reactivation of Herpes Simplex Virus Type 2 from Latently Infected Guinea-pig Neural Tissues by 5-Azacytidine

Enhanced in vitro Reactivation of Herpes Simplex Virus Type 2 from Latently Infected Guinea-pig Neural Tissues by 5-Azacytidine

Is there a role for endogenous retroviruses to mediate long-term adaptive phenotypic response upon environmental inputs?

Binding of the transcription factor EBP-80 mediates the methylation response of an intracisternal A-particle long terminal repeat promoter.

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