@article{8cd3f0eef8da4d5a91ce8d6d8c756c1a,
title = "Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway",
abstract = "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. Jansz et al. report that the chromatin protein Smchd1 depends on polycomb repressive complex 1-mediated ubiquitylation of histone H2A for its recruitment to the inactive X chromosome and for its protein stability. These data have implications for Smchd1 targeting genome-wide.",
keywords = "Hnrnpk, PRC1, Ring1B, Smchd1, X inactivation, Xist",
author = "Natasha Jansz and Tatyana Nesterova and Andrew Keniry and Megan Iminitoff and Hickey, {Peter F.} and Greta Pintacuda and Osamu Masui and Simon Kobelke and Niall Geoghegan and Breslin, {Kelsey A.} and Willson, {Tracy A.} and Kelly Rogers and Kay, {Graham F.} and Fox, {Archa H.} and Haruhiko Koseki and Neil Brockdorff and Murphy, {James M.} and Blewitt, {Marnie E.}",
note = "Funding Information: This work was funded by the Australian National Health and Medical Research Council grant to M.E.B. and J.M.M. (GNT1098290) and fellowship to J.M.M. (GNT1105754). N.J. was supported by an Australian Research Training Program Fellowship. M.E.B. was supported by a Bellberry-Viertel Senior Medical Research Fellowship. This work was made possible through the Victorian State Government Operational Infrastructure Support and the Australian National Health and Medical Research Council Research Institute Infrastructure Support scheme. Funding Information: This work was funded by the Australian National Health and Medical Research Council grant to M.E.B. and J.M.M. ( GNT1098290 ) and fellowship to J.M.M. ( GNT1105754 ). N.J. was supported by an Australian Research Training Program Fellowship . M.E.B. was supported by a Bellberry-Viertel Senior Medical Research Fellowship . This work was made possible through the Victorian State Government Operational Infrastructure Support and the Australian National Health and Medical Research Council Research Institute Infrastructure Support scheme. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = nov,
day = "13",
doi = "10.1016/j.celrep.2018.10.044",
language = "English",
volume = "25",
pages = "1912--1923",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "7",
}