Deletion of Xist Repeat B Disrupts Cell Cycle and Asymmetric Cell Division Through Usp9x Hyperactivation in Mice

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2025 Mar 5

PMID 40042815

Authors

Mingming Liang

Lichao Zhang

Heng Gong

Li Yang

Haijun Wang

Na Song

Liangxue Lai

Wanhua Xie

Zhanjun Li

Affiliations

Soon will be listed here.

Abstract

During X chromosome inactivation (XCI), Xist RNA establishes silencing by coating the chromosome in cis and binding diverse proteins to promote formation of a heterochromatic domain. However, Xist repeat B role beyond initiation of XCI remains unclear. Here, we find that loss of Xist repeat B in female mice allows survival and leads to a small body size persisting throughout life. Epigenetic and transcriptomic analyses reveal low levels of H3K27me3 and H2AK119ub occupancy on the X chromosome, except in certain CpG island regions, and partial reactivation of X-linked genes on the inactive X across multiple tissues. Notably, overdosage of Usp9x promotes centrosome amplification and chromosome instability. We further demonstrate that Usp9x overdosage alters asymmetric cell division, thereby affecting the process of cell differentiation. Thus, Xist repeat B is necessary for gene-specific silencing during XCI maintenance and impacts cell proliferation and differentiation during development. This provides insights into repeat B importance in maintaining XCI.

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