X chromosome inactivation (XCI) is the mammalian mechanism that compensates for the difference in gene dosage between XX females and XY males. Genetic and epigenetic regulatory mechanisms induce transcriptional silencing of one X chromosome in female cells. In mouse embryos, XCI is initiated at the preimplantation stage following early whole-genome activation. It is widely thought that human embryos do not employ XCI prior to implantation. Here, we show that female preimplantation embryos have a progressive accumulation of XIST RNA on one of the two X chromosomes, starting around the 8-cell stage. XIST RNA accumulates at the morula and blastocyst stages and is associated with transcriptional silencing of the XIST-coated chromosomal region. These findings indicate that XCI is initiated in female human preimplantation-stage embryos and suggest that preimplantation dosage compensation is evolutionarily conserved in placental mammals.

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Keywords *Epigenesis, Genetic, Blastocyst/*physiology, Chromosomes, Human, X/*genetics, DNA/genetics, Dosage Compensation, Genetic/*genetics, Embryonic Development, Female, Humans, In Situ Hybridization, Fluorescence, Male, RNA, Untranslated/*genetics, RNA/genetics, X Chromosome Inactivation/*genetics
Persistent URL dx.doi.org/10.1016/j.ajhg.2009.05.003, hdl.handle.net/1765/21002
Citation
van den Berg, I.M, Laven, J.S.E, Stevens, M, Jonkers, I.H, Galjaard, R-J.H, Gribnau, J.H, & van Doorninck, J.H. (2009). X chromosome inactivation is initiated in human preimplantation embryos. American Journal of Human Genetics, 84(6), 771–779. doi:10.1016/j.ajhg.2009.05.003