title: Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice.
abstract: In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene silencing have been the subject of debate. We performed a systematic, single-cell transcriptional analysis to examine the activity of the Xp chromosome for a panel of X-linked genes throughout early preimplantation development in the mouse. Rather than being preinactivated, we found the Xp to be fully active at the time of zygotic gene activation, with silencing beginning from the 4-cell stage onward. X-inactivation patterns were, however, surprisingly diverse between genes. Some loci showed early onset (4-8-cell stage) of X inactivation, and some showed extremely late onset (postblastocyst stage), whereas others were never fully inactivated. Thus, we show that silencing of some X-chromosomal regions occurs outside of the usual time window and that escape from X inactivation can be highly lineage specific. These results reveal that imprinted X inactivation in mice is far less concerted than previously thought and highlight the epigenetic diversity underlying the dosage compensation process during early mammalian development.
authors.affiliation: Mammalian Developmental Epigenetics Group, Institut Curie, Centre National Research Scientifique Unité Mixte de Recherche 3215, Institut National de la Santé et de la Recherche Médicale U934, 75248 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Patrat
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Patricia
authors.initials: P
authors.lastname: Diabangouaya
authors.forename: Vivian
authors.initials: V
authors.lastname: Vialon
authors.forename: Patricia
authors.initials: P
authors.lastname: Le Baccon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chow
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D050172:Genes, X-Linked; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D014158:Transcription, Genetic; D014960:X Chromosome; D049951:X Chromosome Inactivation