About: Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site     Goto   Sponge   NotDistinct   Permalink

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  • The autonomous transcription of integrated retroviruses strongly depends on genetic and epigenetic effects of the chromatin at the site of integration. These effects are mostly suppressive and proviral activity can be finally silenced by mechanisms, such as DNA methylation and histone modifications. To address the role of the integration site at the whole-genome-scale, we performed clonal analysis of provirus silencing with an avian leucosis/sarcoma virus-based reporter vector and correlated the transcriptional silencing with the epigenomic landscape of respective integrations. We demonstrate efficient provirus silencing in human HCT116 cell line, which is strongly but not absolutely dependent on the de novo DNA methyltransferase activity, particularly of Dnmt3b. Proviruses integrated close to the transcription start sites of active genes into the regions enriched in H3K4 trimethylation display long-term stability of expression and are resistant to the transcriptional silencing after over-expression of Dnmt3a or Dnmt3b. In contrast, proviruses in the intergenic regions tend to spontaneous transcriptional silencing even in Dnmt3a(-/-) Dnmt3b(-/-) cells. The silencing of proviruses within genes is accompanied with DNA methylation of long terminal repeats, whereas silencing in intergenic regions is DNA methylation-independent. These findings indicate that the epigenomic features of integration sites are crucial for their permissivity to the proviral expression.
  • The autonomous transcription of integrated retroviruses strongly depends on genetic and epigenetic effects of the chromatin at the site of integration. These effects are mostly suppressive and proviral activity can be finally silenced by mechanisms, such as DNA methylation and histone modifications. To address the role of the integration site at the whole-genome-scale, we performed clonal analysis of provirus silencing with an avian leucosis/sarcoma virus-based reporter vector and correlated the transcriptional silencing with the epigenomic landscape of respective integrations. We demonstrate efficient provirus silencing in human HCT116 cell line, which is strongly but not absolutely dependent on the de novo DNA methyltransferase activity, particularly of Dnmt3b. Proviruses integrated close to the transcription start sites of active genes into the regions enriched in H3K4 trimethylation display long-term stability of expression and are resistant to the transcriptional silencing after over-expression of Dnmt3a or Dnmt3b. In contrast, proviruses in the intergenic regions tend to spontaneous transcriptional silencing even in Dnmt3a(-/-) Dnmt3b(-/-) cells. The silencing of proviruses within genes is accompanied with DNA methylation of long terminal repeats, whereas silencing in intergenic regions is DNA methylation-independent. These findings indicate that the epigenomic features of integration sites are crucial for their permissivity to the proviral expression. (en)
Title
  • Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site
  • Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site (en)
skos:prefLabel
  • Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site
  • Transcriptional provirus silencing as a crosstalk of de novo DNA methylation and epigenomic features at the integration site (en)
skos:notation
  • RIV/68378050:_____/12:00381590!RIV13-GA0-68378050
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(GAP502/11/2207), P(GP301/09/P667), Z(AV0Z50520514)
http://linked.open...iv/cisloPeriodika
  • 12
http://linked.open...vai/riv/dodaniDat
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  • 174853
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  • RIV/68378050:_____/12:00381590
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • retrovirus integration; provirus silencing; epigenomics (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [697A977FA2CA]
http://linked.open...i/riv/nazevZdroje
  • Nucleic Acids Research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 40
http://linked.open...iv/tvurceVysledku
  • Hejnar, Jiří
  • Šenigl, Filip
  • Auxt, Miroslav
http://linked.open...ain/vavai/riv/wos
  • 000305829000019
http://linked.open...n/vavai/riv/zamer
issn
  • 0305-1048
number of pages
http://bibframe.org/vocab/doi
  • 10.1093/nar/gks197
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