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ATRX Promotes Binding of PRC2 to Xist RNA and Polycomb Targets
Author(s) -
Lee Jeannie,
Sarma Kavitha,
CifuentesRojas Catherine,
Ergun Ayla,
Rosario Amanda,
Jeon Yesu,
White Forest,
Sadreyev Ruslan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.361.3
Subject(s) - xist , prc2 , x inactivation , biology , atrx , rna , genetics , chromatin , gene , x chromosome , mutation , histone h3
X‐chromosome inactivation (XCI) depends on the long noncoding RNA Xist and its recruitment of Polycomb Repressive Complex 2 (PRC2). How PRC2 specifically interacts with Xist and other Polycomb targets remains elusive. Using XCI as a model, we take an unbiased proteomics approach to search for new Xist and PRC2 regulators. We identify ATRX and show that ATRX is a high‐affinity RNA‐binding protein that directly interacts with RepA/Xist RNA to promote loading of PRC2 in vivo. The Xist gene is a hotspot of ATRX occupancy. Without ATRX, PRC2 cannot load onto Xist RNA nor spread in cis along the X‐chromosome. Epigenomic profiling reveals a dependency of PRC2 on ATRX that extends beyond XCI. Depleting ATRX results in genome‐wide disruptions to PRC2 localization. PRC2 is displaced from genes and redistributed to intergenic space, causing derepression of Polycomb responsive genes. Thus, ATRX is a required specificity determinant for PRC2 targeting and function.