Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway
Natasha Jansz, Tatyana Nesterova, Andrew Keniry, Megan Iminitoff, Peter F Hickey, Greta Pintacuda, Osamu Masui, Simon Kobelke, Niall Geoghegan, Kelsey A Breslin, Tracy A Willson, Kelly Rogers, Graham F Kay, Archa H Fox, Haruhiko Koseki, Neil Brockdorff, James M Murphy, Marnie E Blewitt
CELL REPORTS | CELL PRESS | Published : 2018
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 genom..View full abstract
Awarded by Australian National Health and Medical Research Council
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.