title: X chromosome inactivation is initiated in human preimplantation embryos.
abstract: 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.
authors.affiliation: Department of Obstetrics & Gynecology, Subdivision of Reproductive Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ilse M
authors.initials: IM
authors.lastname: van den Berg
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Mary
authors.initials: M
authors.lastname: Stevens
authors.forename: Iris
authors.initials: I
authors.lastname: Jonkers
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: Galjaard
authors.forename: Joost
authors.initials: J
authors.lastname: Gribnau
authors.forename: J Hikke
authors.initials: JH
authors.lastname: van Doorninck
mesh_terms: D001755:Blastocyst / Q000502:physiology*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004303:Dosage Compensation, Genetic / Q000235:genetics*; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D012313:RNA / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D012313:RNA; D004247:DNA