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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.

SUBMITTER: Splinter E 

PROVIDER: S-EPMC3134081 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Splinter Erik E   de Wit Elzo E   Nora Elphège P EP   Klous Petra P   van de Werken Harmen J G HJ   Zhu Yun Y   Kaaij Lucas J T LJ   van Ijcken Wilfred W   Gribnau Joost J   Heard Edith E   de Laat Wouter W  

Genes & development 20110620 13


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 sp  ...[more]

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