Xist-mediated Silencing Requires Additive Functions of SPEN and Polycomb Together with Differentiation-dependent Recruitment of SmcHD1

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 May 18

PMID 35584662

Authors

Joseph S Bowness

Tatyana B Nesterova

Guifeng Wei

Lisa Rodermund

Mafalda Almeida

Heather Coker

Emma J Carter

Artun Kadaster

Neil Brockdorff

Affiliations

Soon will be listed here.

Abstract

X chromosome inactivation (XCI) is mediated by the non-coding RNA Xist, which directs chromatin modification and gene silencing in cis. The RNA binding protein SPEN and associated corepressors have a central role in Xist-mediated gene silencing. Other silencing factors, notably the Polycomb system, have been reported to function downstream of SPEN. In recent work, we found that SPEN has an additional role in correct localization of Xist RNA in cis, indicating that its contribution to chromatin-mediated gene silencing needs to be reappraised. Making use of a SPEN separation-of-function mutation, we show that SPEN and Polycomb pathways, in fact, function in parallel to establish gene silencing. We also find that differentiation-dependent recruitment of the chromosomal protein SmcHD1 is required for silencing many X-linked genes. Our results provide important insights into the mechanism of X inactivation and the coordination of chromatin-based gene regulation with cellular differentiation and development.

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