Xist Repeats A and B Account for Two Distinct Phases of X Inactivation Establishment

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2020 Jun 13

PMID 32531209

Citations 23

Authors

David Colognori

Hongjae Sunwoo

Danni Wang

Chen-Yu Wang

Jeannie T Lee

Affiliations

Soon will be listed here.

Abstract

X chromosome inactivation (XCI) is a global silencing mechanism by which XX and XY mammals equalize X-linked gene dosages. XCI begins with an establishment phase during which Xist RNA spreads and induces de novo heterochromatinization across a female X chromosome and is followed by a maintenance phase when multiple epigenetic pathways lock down the inactive X (Xi) state. Involvement of Polycomb repressive complexes 1 and 2 in XCI has been intensively studied but with conflicting conclusions regarding their recruitment and role in Xi silencing. Here, we reveal that establishment of XCI has two phases and reconcile the roles that Xist repeats A and B play in gene silencing and Polycomb recruitment. Repeat A initiates both processes, whereas repeat B bolsters or stabilizes them thereafter. Once established, XCI no longer requires repeat A during maintenance. These findings integrate disparate studies and present a unified view of Xist's role in Polycomb-mediated silencing.

Citing Articles

Deletion of Xist repeat B disrupts cell cycle and asymmetric cell division through Usp9x hyperactivation in mice.

Liang M, Zhang L, Gong H, Yang L, Wang H, Song N Nucleic Acids Res. 2025; 53(5).

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A biophysical basis for the spreading behavior and limited diffusion of Xist.

Ding M, Wang D, Chen H, Kesner B, Grimm N, Weissbein U Cell. 2025; 188(4):978-997.e25.

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Multifaceted role of CTCF in X-chromosome inactivation.

Bammidi L, Gayen S Chromosoma. 2024; 133(4):217-231.

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Re-analysis of CLAP data affirms PRC2 as an RNA binding protein.

Lee Y, Das P, Kesner B, Rosenberg M, Blum R, Lee J bioRxiv. 2024; .

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Xist RNA binds select autosomal genes and depends on Repeat B to regulate their expression.

Yao S, Jeon Y, Kesner B, Lee J bioRxiv. 2024; .

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