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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 languageEnglish
Pages (from-to)1912-1923.e9
JournalCell Reports
Volume25
Issue number7
DOIs
Publication statusPublished - 13 Nov 2018

Fingerprint

Polycomb Repressive Complex 1
X Chromosome
Chromosomes
Genes
Genome
X Chromosome Inactivation
Protein Stability
Homeobox Genes
Ubiquitination
Gene Silencing
Histones
Chromatin
Proteins
RNA
Conformations
Molecules

Cite this

Jansz, N., Nesterova, T., Keniry, A., Iminitoff, M., Hickey, P. F., Pintacuda, G., ... Blewitt, M. E. (2018). Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway. Cell Reports, 25(7), 1912-1923.e9. https://doi.org/10.1016/j.celrep.2018.10.044
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. / Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway. In: Cell Reports. 2018 ; Vol. 25, No. 7. pp. 1912-1923.e9.
@article{ff5a3bcbb1874e2ab3dbcd746c35ba8e,
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.}",
year = "2018",
month = "11",
day = "13",
doi = "10.1016/j.celrep.2018.10.044",
language = "English",
volume = "25",
pages = "1912--1923.e9",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",

}

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 2018, 'Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway' Cell Reports, vol. 25, no. 7, pp. 1912-1923.e9. https://doi.org/10.1016/j.celrep.2018.10.044

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 journalArticle

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 -

Jansz N, Nesterova T, Keniry A, Iminitoff M, Hickey PF, Pintacuda G et al. Smchd1 Targeting to the Inactive X Is Dependent on the Xist-HnrnpK-PRC1 Pathway. Cell Reports. 2018 Nov 13;25(7):1912-1923.e9. https://doi.org/10.1016/j.celrep.2018.10.044