Cell Reports
Volume 25, Issue 7, 13 November 2018, Pages 1912-1923.e9
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Article
Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway

https://doi.org/10.1016/j.celrep.2018.10.044Get rights and content
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Highlights

  • Smchd1 does not bind endogenous RNA with detectable sequence specificity

  • Smchd1 depends on the Xist-HnrpnK-PRC1 pathway for recruitment to the inactive X

  • Smchd1 depends on histone H2A lysine 119 ubiquitination for inactive X localization

  • Smchd1 protein stability depends on histone H2A lysine 119 ubiquitination

Summary

We and others have recently reported that the SMC protein Smchd1 is a regulator of chromosome conformation. Smchd1 is critical for the structure of the inactive X chromosome and at autosomal targets such as the Hox genes. However, it is unknown how Smchd1 is recruited to these sites. Here, we report that Smchd1 localizes to the inactive X via the Xist-HnrnpK-PRC1 (polycomb repressive complex 1) pathway. Contrary to previous reports, Smchd1 does not bind Xist or other RNA molecules with any specificity. Rather, the localization of Smchd1 to the inactive X is H2AK119ub dependent. Following perturbation of this interaction, Smchd1 is destabilized, which has consequences for gene silencing genome-wide. Our work adds Smchd1 to the PRC1 silencing pathway for X chromosome inactivation.

Keywords

Smchd1
X inactivation
Xist
PRC1
Hnrnpk
Ring1B

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