The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA

E. Splinter, E. de Wit, E.P. Nora, P. Klous, H. van de Werken, Y. Zhu, L.J. Kaaij, W. van Ijcken, J. Gribnau, E. Heard, W. de Laat

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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. [KEYWORDS: Animals, Chromosome Structures, Female, Genes, X-Linked/genetics, Mice, RNA, Untranslated/ genetics/metabolism, X Chromosome/ chemistry]
Original languageEnglish
Pages (from-to)1371-1383
JournalGenes & Development
Volume25
Issue number13
DOIs
Publication statusPublished - 2011

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