QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chaumeil, J. Articles by Heard, E. Search for Related Content PubMed PubMed Citation Articles by Chaumeil, J. Articles by Heard, E. Social Bookmarking                   What's this?

A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced

¹ Mammalian Developmental Epigenetic Group, UMR 218, Curie Institute, 75248 Paris Cedex 05, France; ² Mammalian X-chromosome Inactivation Group, Research Institute of Molecular Pathology, A-1030 Vienna, Austria

During early mammalian female development, one of the two X chromosomes becomes inactivated. Although X-chromosome coating by Xist RNA is essential for the initiation of X inactivation, little is known about how this signal is transformed into transcriptional silencing. Here we show that exclusion of RNA Polymerase II and transcription factors from the Xist RNA-coated X chromosome represents the earliest event following Xist RNA accumulation described so far in differentiating embryonic stem (ES) cells. Paradoxically, exclusion of the transcription machinery occurs before gene silencing is complete. However, examination of the three-dimensional organization of X-linked genes reveals that, when transcribed, they are always located at the periphery of, or outside, the Xist RNA domain, in contact with the transcription machinery. Upon silencing, genes shift to a more internal location, within the Xist RNA compartment devoid of transcription factors. Surprisingly, the appearance of this compartment is not dependent on the A-repeats of the Xist transcript, which are essential for gene silencing. However, the A-repeats are required for the relocation of genes into the Xist RNA silent domain. We propose that Xist RNA has multiple functions: A-repeat-independent creation of a transcriptionally silent nuclear compartment; and A-repeat-dependent induction of gene repression, which is associated with their translocation into this silent domain.

[Keywords: X inactivation; Xist RNA; transcriptional silencing; 3D nuclear organization; histone modifications; differentiation]

Received January 22, 2006; revised version accepted June 22, 2006.

E-MAIL Edith.Heard{at}curie.fr; FAX 33-0-1-46-33-30-16.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.380906.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Mohammad, R. R. Pandey, T. Nagano, L. Chakalova, T. Mondal, P. Fraser, and C. Kanduri Kcnq1ot1/Lit1 Noncoding RNA Mediates Transcriptional Silencing by Targeting to the Perinucleolar Region Mol. Cell. Biol., June 1, 2008; 28(11): 3713 - 3728. [Abstract] [Full Text] [PDF]

				A. Rego, P. B. Sinclair, W. Tao, I. Kireev, and A. S. Belmont The facultative heterochromatin of the inactive X chromosome has a distinctive condensed ultrastructure J. Cell Sci., April 1, 2008; 121(7): 1119 - 1127. [Abstract] [Full Text] [PDF]

				R. Schneider and R. Grosschedl Dynamics and interplay of nuclear architecture, genome organization, and gene expression Genes & Dev., December 1, 2007; 21(23): 3027 - 3043. [Abstract] [Full Text] [PDF]

				M. R. Matarazzo, S. Boyle, M. D'Esposito, and W. A. Bickmore Chromosome territory reorganization in a human disease with altered DNA methylation PNAS, October 16, 2007; 104(42): 16546 - 16551. [Abstract] [Full Text] [PDF]

				K. P. Smith, M. Byron, C. Johnson, Y. Xing, and J. B. Lawrence Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains J. Cell Biol., September 7, 2007; 178(6): 951 - 964. [Abstract] [Full Text] [PDF]

				J. C. Chow, L. L. Hall, S. E. L. Baldry, N. P. Thorogood, J. B. Lawrence, and C. J. Brown Inducible XIST-dependent X-chromosome inactivation in human somatic cells is reversible PNAS, June 12, 2007; 104(24): 10104 - 10109. [Abstract] [Full Text] [PDF]

				A. Vincent-Salomon, C. Ganem-Elbaz, E. Manie, V. Raynal, X. Sastre-Garau, D. Stoppa-Lyonnet, M.-H. Stern, and E. Heard X Inactive-Specific Transcript RNA Coating and Genetic Instability of the X Chromosome in BRCA1 Breast Tumors Cancer Res., June 1, 2007; 67(11): 5134 - 5140. [Abstract] [Full Text] [PDF]

				H. Barr, A. Hermann, J. Berger, H.-H. Tsai, K. Adie, A. Prokhortchouk, B. Hendrich, and A. Bird Mbd2 Contributes to DNA Methylation-Directed Repression of the Xist Gene Mol. Cell. Biol., May 15, 2007; 27(10): 3750 - 3757. [Abstract] [Full Text] [PDF]

				K. V. Prasanth and D. L. Spector Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum Genes & Dev., January 1, 2007; 21(1): 11 - 42. [Abstract] [Full Text] [PDF]

				N. LeBrasseur A transcriptional black hole J. Cell Biol., September 25, 2006; 174(7): 908 - 908. [Full Text] [PDF]