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Disruption of ATRX-RNA interactions uncovers roles in ATRX localization and PRC2 function

Author

Listed:
  • Wenqing Ren

    (The Wistar Institute
    University of Pennsylvania)

  • Nicole Medeiros

    (The Wistar Institute
    University of Pennsylvania)

  • Robert Warneford-Thomson

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Phillip Wulfridge

    (The Wistar Institute
    University of Pennsylvania)

  • Qingqing Yan

    (The Wistar Institute
    University of Pennsylvania)

  • Joyce Bian

    (The Wistar Institute
    University of Pennsylvania)

  • Simone Sidoli

    (University of Pennsylvania
    University of Pennsylvania
    Albert Einstein College of Medicine)

  • Benjamin A. Garcia

    (University of Pennsylvania
    University of Pennsylvania)

  • Emmanuel Skordalakes

    (The Wistar Institute)

  • Eric Joyce

    (University of Pennsylvania
    University of Pennsylvania)

  • Roberto Bonasio

    (University of Pennsylvania
    University of Pennsylvania)

  • Kavitha Sarma

    (The Wistar Institute
    University of Pennsylvania)

Abstract

Heterochromatin in the eukaryotic genome is rigorously controlled by the concerted action of protein factors and RNAs. Here, we investigate the RNA binding function of ATRX, a chromatin remodeler with roles in silencing of repetitive regions of the genome and in recruitment of the polycomb repressive complex 2 (PRC2). We identify ATRX RNA binding regions (RBRs) and discover that the major ATRX RBR lies within the N-terminal region of the protein, distinct from its PHD and helicase domains. Deletion of this ATRX RBR (ATRXΔRBR) compromises ATRX interactions with RNAs in vitro and in vivo and alters its chromatin binding properties. Genome-wide studies reveal that loss of RNA interactions results in a redistribution of ATRX on chromatin. Finally, our studies identify a role for ATRX-RNA interactions in regulating PRC2 localization to a subset of polycomb target genes.

Suggested Citation

  • Wenqing Ren & Nicole Medeiros & Robert Warneford-Thomson & Phillip Wulfridge & Qingqing Yan & Joyce Bian & Simone Sidoli & Benjamin A. Garcia & Emmanuel Skordalakes & Eric Joyce & Roberto Bonasio & Ka, 2020. "Disruption of ATRX-RNA interactions uncovers roles in ATRX localization and PRC2 function," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15902-9
    DOI: 10.1038/s41467-020-15902-9
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