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

E Splinter, E de Wit, EP Nora, P Klous… - Genes & …, 2011 - genesdev.cshlp.org
E Splinter, E de Wit, EP Nora, P Klous, HJG van de Werken, Y Zhu, LJT Kaaij, W van IJcken
Genes & development, 2011genesdev.cshlp.org
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 …
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.
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