title: Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development.
abstract: X-chromosome inactivation (XCI) in female mammals allows dosage compensation for X-linked gene products between the sexes. The developmental regulation of this process has been extensively investigated in mice, where the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript). Paternal XCI is reversed in the inner cell mass of the blastocyst and random XCI subsequently occurs in epiblast cells. Here we show that other eutherian mammals have very different strategies for initiating XCI. In rabbits and humans, the Xist homologue is not subject to imprinting and XCI begins later than in mice. Furthermore, Xist is upregulated on both X chromosomes in a high proportion of rabbit and human embryo cells, even in the inner cell mass. In rabbits, this triggers XCI on both X chromosomes in some cells. In humans, chromosome-wide XCI has not initiated even by the blastocyst stage, despite the upregulation of XIST. The choice of which X chromosome will finally become inactive thus occurs downstream of Xist upregulation in both rabbits and humans, unlike in mice. Our study demonstrates the remarkable diversity in XCI regulation and highlights differences between mammals in their requirement for dosage compensation during early embryogenesis.
authors.affiliation: Mammalian Developmental Epigenetics Group, Institut Curie, CNRS UMR 3215, INSERM U934, Paris 75248, France.
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Catherine
authors.initials: C
authors.lastname: Patrat
authors.forename: Dominique
authors.initials: D
authors.lastname: Thépot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Peynot
authors.forename: Patricia
authors.initials: P
authors.lastname: Fauque
authors.forename: Nathalie
authors.initials: N
authors.lastname: Daniel
authors.forename: Patricia
authors.initials: P
authors.lastname: Diabangouaya
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Wolf
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Renard
authors.forename: Véronique
authors.initials: V
authors.lastname: Duranthon
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001755:Blastocyst / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004303:Dosage Compensation, Genetic / Q000235:genetics; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D050172:Genes, X-Linked / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D008322:Mammals / Q000196:embryology / Q000235:genetics*; D051379:Mice; D010312:Parthenogenesis; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D011817:Rabbits; D013045:Species Specificity; D015854:Up-Regulation / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D007041:Hypoxanthine Phosphoribosyltransferase