Defects in dosage compensation impact global gene regulation in the mouse trophoblast

Yuka Sakata, Koji Nagao, Yuko Hoki, Hiroyuki Sasaki, Chikashi Obuse, Takashi Sado

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Xist RNA, which is responsible for X inactivation, is a key epigenetic player in the embryogenesis of female mammals. Of the several repeats conserved in Xist RNA, the A-repeat has been shown to be essential for its silencing function in differentiating embryonic stem cells. Here, we introduced a new Xist allele into mouse that produces mutated Xist RNA lacking the A-repeat (XistCAGΔ5′). XistCAGΔ5′ RNA expressed in the embryo coated the X chromosome but failed to silence it. Although imprinted X inactivation was substantially compromised upon paternal transmission, allele-specific RNA-seq in the trophoblast revealed that XistCAGΔ5′ RNA still retained some silencing ability. Furthermore, the failure of imprinted X inactivation had more significant impacts than expected on genome-wide gene expression. It is likely that dosage compensation is required not only for equalizing X-linked gene expression between the sexes but also for proper global gene regulation in differentiated female somatic cells.

Original languageEnglish
Pages (from-to)2784-2797
Number of pages14
JournalDevelopment (Cambridge)
Volume144
Issue number15
DOIs
Publication statusPublished - Aug 1 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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