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PRC1 collaborates with SMCHD1 to fold the X-chromosome and spread Xist RNA between chromosome compartments

Chen-Yu Wang, David Colognori, Hongjae Sunwoo, Danni Wang and Jeannie T. Lee ()
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Chen-Yu Wang: Massachusetts General Hospital
David Colognori: Massachusetts General Hospital
Hongjae Sunwoo: Massachusetts General Hospital
Danni Wang: Massachusetts General Hospital
Jeannie T. Lee: Massachusetts General Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: Abstract X-chromosome inactivation triggers fusion of A/B compartments to inactive X (Xi)-specific structures known as S1 and S2 compartments. SMCHD1 then merges S1/S2s to form the Xi super-structure. Here, we ask how S1/S2 compartments form and reveal that Xist RNA drives their formation via recruitment of Polycomb repressive complex 1 (PRC1). Ablating Smchd1 in post-XCI cells unveils S1/S2 structures. Loss of SMCHD1 leads to trapping Xist in the S1 compartment, impairing RNA spreading into S2. On the other hand, depleting Xist, PRC1, or HNRNPK precludes re-emergence of S1/S2 structures, and loss of S1/S2 compartments paradoxically strengthens the partition between Xi megadomains. Finally, Xi-reactivation in post-XCI cells can be enhanced by depleting both SMCHD1 and DNA methylation. We conclude that Xist, PRC1, and SMCHD1 collaborate in an obligatory, sequential manner to partition, fuse, and direct self-association of Xi compartments required for proper spreading of Xist RNA.

Date: 2019
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DOI: 10.1038/s41467-019-10755-3

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