TY - JOUR
T1 - Defects in dosage compensation impact global gene regulation in the mouse trophoblast
AU - Sakata, Yuka
AU - Nagao, Koji
AU - Hoki, Yuko
AU - Sasaki, Hiroyuki
AU - Obuse, Chikashi
AU - Sado, Takashi
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas (26113714 and 16H01320 to T.S.; 15K06942 and 15H01462 to K.N.; and 25116004 to C.O.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT).
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
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U2 - 10.1242/dev.149138
DO - 10.1242/dev.149138
M3 - Article
C2 - 28684628
AN - SCOPUS:85026777436
VL - 144
SP - 2784
EP - 2797
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 15
ER -