PRC1 与 SMCHD1 合作折叠 X 染色体，并在染色体隔室之间散布 Xist RNA。
PRC1 collaborates with SMCHD1 to fold the X-chromosome and spread Xist RNA between chromosome compartments.
机构信息
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
出版信息
Nat Commun. 2019 Jul 3;10(1):2950. doi: 10.1038/s41467-019-10755-3.
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.
X 染色体失活触发 A/B 区室融合为失活 X（Xi）特异性结构，称为 S1 和 S2 区室。然后，SMCHD1 将 S1/S2 合并形成 Xi 超结构。在这里，我们想知道 S1/S2 区室是如何形成的，并揭示 Xist RNA 通过募集多梳抑制复合物 1（PRC1）来驱动它们的形成。在 XCI 后细胞中敲除 Smchd1 会揭示 S1/S2 结构。SMCHD1 的缺失导致 Xist 被困在 S1 区室中，阻碍 RNA 扩散到 S2 中。另一方面，耗尽 Xist、PRC1 或 HNRNPK 会阻止 S1/S2 结构的重新出现，而 S1/S2 区室的缺失反而会增强 Xi 巨域之间的分隔。最后，在 XCI 后细胞中耗尽 SMCHD1 和 DNA 甲基化可以增强 Xi 的重新激活。我们得出结论，Xist、PRC1 和 SMCHD1 以必需的、连续的方式协作，对 Xi 区室进行分隔、融合和定向自身组装，以实现 Xist RNA 的正确扩散。
Zotero 插件