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 and Development
JF - Genes and Development
IS - 13
ER -