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 and Kavitha Sarma ()
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Wenqing Ren: The Wistar Institute
Nicole Medeiros: The Wistar Institute
Robert Warneford-Thomson: University of Pennsylvania
Phillip Wulfridge: The Wistar Institute
Qingqing Yan: The Wistar Institute
Joyce Bian: The Wistar Institute
Simone Sidoli: University of Pennsylvania
Benjamin A. Garcia: University of Pennsylvania
Emmanuel Skordalakes: The Wistar Institute
Eric Joyce: University of Pennsylvania
Roberto Bonasio: University of Pennsylvania
Kavitha Sarma: The Wistar Institute

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15902-9

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