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.
| Original language | English |
|---|---|
| Pages (from-to) | 1912-1923.e9 |
| Journal | Cell Reports |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 13 Nov 2018 |
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Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway. / Jansz, Natasha; Nesterova, Tatyana; Keniry, Andrew; Iminitoff, Megan; Hickey, Peter F.; Pintacuda, Greta; Masui, Osamu; Kobelke, Simon; Geoghegan, Niall; Breslin, Kelsey A.; Willson, Tracy A.; Rogers, Kelly; Kay, Graham F.; Fox, Archa H.; Koseki, Haruhiko; Brockdorff, Neil; Murphy, James M.; Blewitt, Marnie E.
In: Cell Reports, Vol. 25, No. 7, 13.11.2018, p. 1912-1923.e9.Research output: Contribution to journal › Article
TY - JOUR
T1 - Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway
AU - Jansz, Natasha
AU - Nesterova, Tatyana
AU - Keniry, Andrew
AU - Iminitoff, Megan
AU - Hickey, Peter F.
AU - Pintacuda, Greta
AU - Masui, Osamu
AU - Kobelke, Simon
AU - Geoghegan, Niall
AU - Breslin, Kelsey A.
AU - Willson, Tracy A.
AU - Rogers, Kelly
AU - Kay, Graham F.
AU - Fox, Archa H.
AU - Koseki, Haruhiko
AU - Brockdorff, Neil
AU - Murphy, James M.
AU - Blewitt, Marnie E.
PY - 2018/11/13
Y1 - 2018/11/13
N2 - 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.
AB - 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.
KW - Hnrnpk
KW - PRC1
KW - Ring1B
KW - Smchd1
KW - X inactivation
KW - Xist
UR - http://www.scopus.com/inward/record.url?scp=85056183030&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.10.044
DO - 10.1016/j.celrep.2018.10.044
M3 - Article
VL - 25
SP - 1912-1923.e9
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 7
ER -