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

Wenqing Ren, Nicole Medeiros, Robert Warneford-Thomson, Phillip Wulfridge, Qingqing Yan, Joyce Bian, Simone Sidoli, Benjamin A. Garcia, Emmanuel Skordalakes, Eric Joyce, Roberto Bonasio, Kavitha Sarma

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number2219
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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