Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway

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...

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Main Authors: 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
Format: Journal article
Language:English
Published: Elsevier 2018
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author 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
author_facet 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
author_sort Jansz, N
collection OXFORD
description 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.
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spelling oxford-uuid:99cd97a6-d9e5-4380-82a9-c3283b9242e52022-03-27T00:17:00ZSmchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathwayJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:99cd97a6-d9e5-4380-82a9-c3283b9242e5EnglishSymplectic ElementsElsevier2018Jansz, NNesterova, TKeniry, AIminitoff, MHickey, PFPintacuda, GMasui, OKobelke, SGeoghegan, NBreslin, KAWillson, TARogers, KKay, GFFox, AHKoseki, HBrockdorff, NMurphy, JMBlewitt, MEWe 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.
spellingShingle 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
Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway
title Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway
title_full Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway
title_fullStr Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway
title_full_unstemmed Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway
title_short Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway
title_sort smchd1 targeting to the inactive x is dependent on the xist hnrnpk prc1 pathway
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