Nature Cell Biology 8, 293 - 299 (2006)
Published online: 24 January 2006; | doi:10.1038/ncb1365
Transient colocalization of X-inactivation centres accompanies the initiation of X inactivationChristian P. Bacher1, Michèle Guggiari2, Benedikt Brors1, Sandrine Augui2, Philippe Clerc3, Philip Avner3, Roland Eils1, 4, 5
& Edith Heard2, 51
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, German. 2
CNRS UMR 218, Curie Institute, 26 rue d'Ulm, 75248 Paris Cedex 05, France. 3
Pasteur Institute, 25 rue du Docteur Roux, Paris 75015, France. 4
Institute of Pharmacy and Molecular Biotechnology (IPMB), University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. 5
These authors contributed equally to this work.
Correspondence should be addressed to Edith Heard Edith.Heard@curie.fr or Roland Eils r.eils@dkfz-heidelberg.de 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.
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