A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-oforigin effects

Yuko Amakawa, Yuka Sakata, Yuko Hoki, Satoru Arata, Seiji Shioda, Tatsuo Fukagawa, Hiroyuki Sasaki, Takashi Sado

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    Abstract

    The dosage difference of X-linked genes between the sexes in mammals is compensated for by genetic inactivation of one of the X chromosomes in XX females. A noncoding RNA transcribed from the Xist gene at the onset of X chromosome inactivation coats the X chromosome in cis and induces chromosome-wide heterochromatinization. Here, we report a new Xist allele (XistCAG) driven by a CAG promoter, which is known to be constitutively active in many types of cells. The paternal transmission of XistCAG resulted in the preferential inactivation of the targeted paternal X (Xp) not only in the extra-embryonic but also the embryonic lineage, whereas maternal transmission ended with embryonic lethality at the early postimplantation stage with a phenotype that resembled mutant embryos carrying a maternal deficiency in Tsix, an antisense negative regulator of Xist, in both sexes. Interestingly, we found that the upregulation of XistCAG in preimplantation embryos temporally differed depending on its parental origin: its expression started at the 4- to 8-cell stages when paternally inherited, and XistCAG was upregulated at the blastocyst stage when maternally inherited. This might indicate that the Xist locus on Xp is permissive to transcription, but the Xist locus on the maternal X (Xm) is not.We extrapolated from these findings that the maternal Xist allele might manifest a chromatin structure inaccessible by transcription factors relative to the paternal allele. This might underlie the mechanism for the maternal repression of Xist at the early cleavage stage when Tsix expression has not yet occurred on Xm.

    Original languageEnglish
    Pages (from-to)4299-4308
    Number of pages10
    JournalDevelopment (Cambridge)
    Volume142
    Issue number24
    DOIs
    Publication statusPublished - Dec 15 2015

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    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Developmental Biology

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