TY - JOUR
T1 - Disruption of ATRX-RNA interactions uncovers roles in ATRX localization and PRC2 function
AU - Ren, Wenqing
AU - Medeiros, Nicole
AU - Warneford-Thomson, Robert
AU - Wulfridge, Phillip
AU - Yan, Qingqing
AU - Bian, Joyce
AU - Sidoli, Simone
AU - Garcia, Benjamin A.
AU - Skordalakes, Emmanuel
AU - Joyce, Eric
AU - Bonasio, Roberto
AU - Sarma, Kavitha
N1 - Funding Information:
We thank all lab members for helpful discussions. We thank T. de lange for ATRX knock out MEFs. This work was supported by National Institutes of Health Grant DP2-NS105576 (to K.S.). R.B. acknowledges support from the NIH (R01GM127408) and the March of Dimes Foundation (1-FY-15-344). B.A.G. acknowledges support from the NIH (GM110174 and CA196539). R.W.T. was supported by NIH training grant T32GM008216.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-15902-9
DO - 10.1038/s41467-020-15902-9
M3 - Article
C2 - 32376827
AN - SCOPUS:85084391456
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2219
ER -