title: The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA.
abstract: Three-dimensional topology of DNA in the cell nucleus provides a level of transcription regulation beyond the sequence of the linear DNA. To study the relationship between the transcriptional activity and the spatial environment of a gene, we used allele-specific chromosome conformation capture-on-chip (4C) technology to produce high-resolution topology maps of the active and inactive X chromosomes in female cells. We found that loci on the active X form multiple long-range interactions, with spatial segregation of active and inactive chromatin. On the inactive X, silenced loci lack preferred interactions, suggesting a unique random organization inside the inactive territory. However, escapees, among which is Xist, are engaged in long-range contacts with each other, enabling identification of novel escapees. Deletion of Xist results in partial refolding of the inactive X into a conformation resembling the active X without affecting gene silencing or DNA methylation. Our data point to a role for Xist RNA in shaping the conformation of the inactive X chromosome at least partially independent of transcription.
authors.affiliation: Hubrecht Institute-KNAW, University Medical Center Utrecht, Utrecht 3584 CT, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Splinter
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.forename: Elphège P
authors.initials: EP
authors.lastname: Nora
authors.forename: Petra
authors.initials: P
authors.lastname: Klous
authors.forename: Harmen J G
authors.initials: HJ
authors.lastname: van de Werken
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lucas J T
authors.initials: LJ
authors.lastname: Kaaij
authors.forename: Wilfred
authors.initials: W
authors.lastname: van Ijcken
authors.forename: Joost
authors.initials: J
authors.lastname: Gribnau
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
mesh_terms: D000818:Animals; D022004:Chromosome Structures; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D051379:Mice; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D014960:X Chromosome / Q000737:chemistry*
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA