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The anti-cancer drugs curaxins target spatial genome organization

Author

Listed:
  • Omar L. Kantidze

    (Institute of Gene Biology RAS)

  • Artem V. Luzhin

    (Institute of Gene Biology RAS)

  • Ekaterina V. Nizovtseva

    (Cancer Epigenetics Program, Fox Chase Cancer Center)

  • Alfiya Safina

    (Roswell Park Comprehensive Cancer Center)

  • Maria E. Valieva

    (Lomonosov Moscow State University)

  • Arkadiy K. Golov

    (Institute of Gene Biology RAS)

  • Artem K. Velichko

    (Institute of Gene Biology RAS)

  • Alexander V. Lyubitelev

    (Lomonosov Moscow State University)

  • Alexey V. Feofanov

    (Lomonosov Moscow State University
    Russian Academy of Sciences)

  • Katerina V. Gurova

    (Roswell Park Comprehensive Cancer Center)

  • Vasily M. Studitsky

    (Cancer Epigenetics Program, Fox Chase Cancer Center
    Lomonosov Moscow State University)

  • Sergey V. Razin

    (Institute of Gene Biology RAS
    Lomonosov Moscow State University)

Abstract

Recently we characterized a class of anti-cancer agents (curaxins) that disturbs DNA/histone interactions within nucleosomes. Here, using a combination of genomic and in vitro approaches, we demonstrate that curaxins strongly affect spatial genome organization and compromise enhancer-promoter communication, which is necessary for the expression of several oncogenes, including MYC. We further show that curaxins selectively inhibit enhancer-regulated transcription of chromatinized templates in cell-free conditions. Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. Thus, curaxins can be classified as epigenetic drugs that target the 3D genome organization.

Suggested Citation

  • Omar L. Kantidze & Artem V. Luzhin & Ekaterina V. Nizovtseva & Alfiya Safina & Maria E. Valieva & Arkadiy K. Golov & Artem K. Velichko & Alexander V. Lyubitelev & Alexey V. Feofanov & Katerina V. Guro, 2019. "The anti-cancer drugs curaxins target spatial genome organization," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09500-7
    DOI: 10.1038/s41467-019-09500-7
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