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

TY - JOUR

T1 - The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA

AU - Splinter, E.

AU - de Wit, E.

AU - Nora, E.P.

AU - Klous, P.

AU - van de Werken, H.

AU - Zhu, Y.

AU - Kaaij, L.J.

AU - van Ijcken, W.

AU - Gribnau, J.

AU - Heard, E.

AU - de Laat, W.

N1 - Reporting year: 2011 Metis note: 3134081;

PY - 2011

Y1 - 2011

N2 - 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]

AB - 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]

U2 - 10.1101/gad.633311

DO - 10.1101/gad.633311

M3 - Article

SN - 0890-9369

VL - 25

SP - 1371

EP - 1383

JO - Genes & Development

JF - Genes & Development

IS - 13

ER -