title: Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation.
abstract: Random X inactivation represents a paradigm for monoallelic gene regulation during early ES cell differentiation. In mice, the choice of X chromosome to inactivate in XX cells is ensured by monoallelic regulation of Xist RNA via its antisense transcription unit Tsix/Xite. Homologous pairing events have been proposed to underlie asymmetric Tsix expression, but direct evidence has been lacking owing to their dynamic and transient nature. Here we investigate the live-cell dynamics and outcome of Tsix pairing in differentiating mouse ES cells. We find an overall increase in genome dynamics including the Xics during early differentiation. During pairing, however, Xic loci show markedly reduced movements. Upon separation, Tsix expression becomes transiently monoallelic, providing a window of opportunity for monoallelic Xist upregulation. Our findings reveal the spatiotemporal choreography of the X chromosomes during early differentiation and indicate a direct role for pairing in facilitating symmetry-breaking and monoallelic regulation of Xist during random X inactivation.
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Osamu
authors.initials: O
authors.lastname: Masui
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bonnet
authors.forename: Patricia
authors.initials: P
authors.lastname: Le Baccon
authors.forename: Isabel
authors.initials: I
authors.lastname: Brito
authors.forename: Tim
authors.initials: T
authors.lastname: Pollex
authors.forename: Niall
authors.initials: N
authors.lastname: Murphy
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Belmont
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D023902:Chromosome Pairing; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D051379:Mice; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D059008:Time-Lapse Imaging; D014960:X Chromosome / Q000378:metabolism*; D049951:X Chromosome Inactivation
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C465658:Tsix transcript, mouse