Smchd1 Targeting to the Inactive X Is dependent on the Xist-HnrnpK-PRC1 pathway
- Jansz, N; Nesterova, T; Keniry, A; Iminitoff, M; Hickey, PF; Pintacuda, G; Masui, O; Kobelke, S; Geoghegan, N; Breslin, KA; Willson, TA; Rogers, K; Kay, GF; Fox, AH; Koseki, H; Brockdorff, N; Murphy, JM; Blewitt, ME;
Publication Year 2018-11-13, Volume 25, Issue #7, Page 1912-1923 e9
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- 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.
- WEHI Research Division(s)
- Molecular Medicine; Systems Biology And Personalised Medicine; Cell Signalling And Cell Death
- PubMed ID
- Publisher's Version
- Open Access at Publisher's Site
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-11-20 03:13:38Last Modified: 2018-11-20 03:14:54