title: Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation.
abstract: The initial differential treatment of the two X chromosomes during X-chromosome inactivation is controlled by the X-inactivation centre (Xic). This locus determines how many X chromosomes are present in a cell ('counting') and which X chromosome will be inactivated in female cells ('choice'). Critical control sequences in the Xic include the non-coding RNAs Xist and Tsix, and long-range chromatin elements. However, little is known about the process that ensures that X inactivation is triggered appropriately when more than one Xic is present in a cell. Using three-dimensional fluorescence in situ hybridization (FISH) analysis, we showed that the two Xics transiently colocalize, just before X inactivation, in differentiating female embryonic stem cells. Using Xic transgenes capable of imprinted but not random X inactivation, and Xic deletions that disrupt random X inactivation, we demonstrated that Xic colocalization is linked to Xic function in random X inactivation. Both long-range sequences and the Tsix element, which generates the antisense transcript to Xist, are required for the transient interaction of Xics. We propose that transient colocalization of Xics may be necessary for a cell to determine Xic number and to ensure the correct initiation of X inactivation.
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, German.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Bacher
authors.forename: Michèle
authors.initials: M
authors.lastname: Guggiari
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.forename: Sandrine
authors.initials: S
authors.lastname: Augui
authors.forename: Philippe
authors.initials: P
authors.lastname: Clerc
authors.forename: Philip
authors.initials: P
authors.lastname: Avner
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D018392:Genomic Imprinting; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D014960:X Chromosome / Q000502:physiology*; D049951:X Chromosome Inactivation
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA