PMID- 16434960 OWN - NLM STAT- MEDLINE DCOM- 20060501 LR - 20131121 IS - 1465-7392 (Print) IS - 1465-7392 (Linking) VI - 8 IP - 3 DP - 2006 Mar TI - Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. PG - 293-9 AB - 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. FAU - Bacher, Christian P AU - Bacher CP AD - German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, German. FAU - Guggiari, Michele AU - Guggiari M FAU - Brors, Benedikt AU - Brors B FAU - Augui, Sandrine AU - Augui S FAU - Clerc, Philippe AU - Clerc P FAU - Avner, Philip AU - Avner P FAU - Eils, Roland AU - Eils R FAU - Heard, Edith AU - Heard E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060124 PL - England TA - Nat Cell Biol JT - Nature cell biology JID - 100890575 RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Untranslated) RN - 0 (XIST non-coding RNA) SB - IM CIN - Nat Cell Biol. 2006 Mar;8(3):207-9. PMID: 16508671 MH - Animals MH - Cell Differentiation MH - Cells, Cultured MH - Embryo, Mammalian/cytology MH - Female MH - *Genomic Imprinting MH - In Situ Hybridization, Fluorescence MH - Male MH - Mice MH - RNA, Long Noncoding MH - RNA, Untranslated/genetics/*physiology MH - Stem Cells/*physiology MH - X Chromosome/*physiology MH - *X Chromosome Inactivation EDAT- 2006/01/26 09:00 MHDA- 2006/05/02 09:00 CRDT- 2006/01/26 09:00 PHST- 2005/10/31 00:00 [received] PHST- 2006/01/11 00:00 [accepted] PHST- 2006/01/26 09:00 [pubmed] PHST- 2006/05/02 09:00 [medline] PHST- 2006/01/26 09:00 [entrez] AID - ncb1365 [pii] AID - 10.1038/ncb1365 [doi] PST - ppublish SO - Nat Cell Biol. 2006 Mar;8(3):293-9. doi: 10.1038/ncb1365. Epub 2006 Jan 24.