Journal Article

DKFZ-2025-02962

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Escape from X inactivation is directly modulated by Xist noncoding RNA.

Hauth, A. ; Panten, J. (First author)DKFZ* ; Kneuss, E. ; Picard, C. ; Servant, N. ; Rall, I. ; Pérez-Rico, Y. A. ; Clerquin, L. ; Servaas, N. ; Villacorta, L. ; Jung, F. ; Luong, C. ; Chang, H. Y. ; Zaugg, J. B. ; Stegle, O.DKFZ* ; Odom, D.DKFZ* ; Heard, E. ; Loda, A.

2026
Nature America New York, NY

Abstract: In placental XX females, one X chromosome is silenced during a narrow developmental time window by X-chromosome inactivation, which is mediated by Xist noncoding RNA. Although most X-linked genes are silenced during X-chromosome inactivation, some genes can escape. Here, by increasing its endogenous level, we show that Xist RNA can silence escapees well beyond early embryogenesis both in vitro, in differentiated cells, as well as in vivo, in mouse pre- and post-implantation embryos. We further demonstrate that Xist RNA plays a role in eliminating topologically associating domain-like structures spanning clusters of escapees, and this is dependent on SPEN. The function of Xist in silencing escapees and eliminating topological domains is initially fully reversible, but sustained Xist upregulation leads to irreversible silencing and CpG island DNA methylation of escapees. Thus, gene activity and three-dimensional topology of the inactive X chromosome are directly controlled by Xist, well beyond an early developmental time window.

Note: #EA:B270#LA:B270# / 2026 Jan;28(1):166-181

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Contributing Institute(s):

1. B270 Regulatorische Genomik und Evolution von Tumoren (B270)
2. B260 Bioinformatik der Genomik und Systemgenetik (B260)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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