The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA
- Erik Splinter1,
- Elzo de Wit1,
- Elphège P. Nora2,3,4,
- Petra Klous1,
- Harmen J.G. van de Werken1,
- Yun Zhu1,
- Lucas J.T. Kaaij1,
- Wilfred van IJcken5,
- Joost Gribnau6,
- Edith Heard2 and
- Wouter de Laat1,7
- 1Hubrecht Institute-KNAW, University Medical Center Utrecht, Utrecht 3584 CT, The Netherlands;
- 2Mammalian Developmental Epigenetics Group, Institut Curie, Paris F-75248, France;
- 3CNRS, UMR3215, Paris F-75248, France;
- 4INSERM, U934, Paris F-75248, France;
- 5Erasmus Center of Biomics, Erasmus Medical Center, Rotterdam 3015 GE, The Netherlands;
- 6Department of Reproduction and Development, Erasmus Medical Center, Rotterdam 3015 GE, The Netherlands
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.
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Footnotes
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↵7 Corresponding author.
E-mail w.laat{at}hubrecht.eu.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.633311.
- Received April 1, 2011.
- Accepted May 25, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press