X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels

Ryan N. Allsop, Jeffrey Boeren, Beatrice F. Tan, Sarra Merzouk, Suresh Poovanthingal, Wilfred F. J. IJcken, Jeroen A. A. Demmers, Hegias Mira Bontenbal, Cristina Gontan, Joost Gribnau () and Vincent Pasque ()
Additional contact information
Ryan N. Allsop: University of Leuven (KU Leuven)
Jeffrey Boeren: Erasmus University Medical Center
Beatrice F. Tan: Erasmus University Medical Center
Sarra Merzouk: Erasmus University Medical Center
Suresh Poovanthingal: KU Leuven Institute for Single Cell Omics (LISCO)
Wilfred F. J. IJcken: Erasmus University Medical Center
Jeroen A. A. Demmers: Erasmus University Medical Center
Hegias Mira Bontenbal: Erasmus University Medical Center
Cristina Gontan: Erasmus University Medical Center
Joost Gribnau: Erasmus University Medical Center
Vincent Pasque: University of Leuven (KU Leuven)

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Gene dosage compensation mechanisms are crucial for mammalian development. In mice, recent findings show that cells can sense the number of X chromosomes. Loss or inactivation of one of the two X chromosomes is compensated by upregulating the remaining active X chromosome, a process termed X-chromosome upregulation (XCU). However, how cells sense X-chromosome dosage and induce XCU remains unclear. Here, we show that heterozygous X chromosome fragment deletions in mouse pluripotent stem cells induces XCU in trans, and that compensation takes place at the mRNA and protein level. Furthermore, we found that inducing gene silencing in cis on autosomes induces gene dosage compensation in trans. This work provides significant insights into the molecular foundations of mammalian gene dosage compensation.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64195-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64195-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64195-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().