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<p>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 <i>in cis</i> on autosomes induces gene dosage compensation in trans. This work provides significant insights into the molecular foundations of mammalian gene dosage compensation.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Ryan N. Allsop,
  • Jeffrey Boeren,
  • Beatrice F. Tan,
  • Sarra Merzouk,
  • Suresh Poovanthingal,
  • Wilfred F. J. van IJcken,
  • Jeroen A. A. Demmers,
  • Hegias Mira Bontenbal,
  • Cristina Gontan,
  • Joost Gribnau,
  • Vincent Pasque

摘要

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.