Open AccessDefects in dosage compensation impact global gene regulation in the mouse trophoblast
Author(s) -
Yuka Sakata,
Koji Nagao,
Yuko Hoki,
Hidetada Sasaki,
Chikashi Obuse,
Takashi Sado
Publication year - 2017
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.149138
Subject(s) - biology , trophoblast , dosage compensation , gene dosage , gene , microbiology and biotechnology , genetics , computational biology , gene expression , placenta , pregnancy , fetus
Xist RNA responsible for X inactivation is one of the most important epigenetic players for 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 ES cells. Here, we introduced a new Xist allele into the mouse, which 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 gene expression genome-wide. It is likely that dosage compensation is required for not only equalizing the X-linked gene expression between the sexes but also proper global gene regulation in differentiated female somatic cells.