© The Rockefeller University Press,
0021-9525/1998//13 $5.00
The Journal of Cell Biology, Volume 142, Number 1,
, 1998 13-23
Stabilization and Localization of Xist RNA are Controlled by Separate Mechanisms and are Not Sufficient for X Inactivation
Christine Moulton Clemson*,
Jennifer C. Chow
,
Carolyn J. Brown
, and
Jeanne Bentley Lawrence*
* Department of Cell Biology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655; and
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V6T1Z3
These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935–2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chromosomes in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite their inability to localize, and hence XIST RNA localization can be uncoupled from stabilization, indicating that these are separate steps controlled by distinct mechanisms. Mouse Xist RNA tightly localized to an active X chromosome, demonstrating for the first time that the active X chromosome in somatic cells is competent to associate with Xist RNA. These results imply that species-specific factors, present even in mature, somatic cells that do not normally express Xist, are necessary for localization. When Xist RNA is properly localized to an active mouse X chromosome, X inactivation does not result. Therefore, there is not a strict correlation between Xist localization and chromatin inactivation. Moreover, expression, stabilization, and localization of Xist RNA are not sufficient for X inactivation. We hypothesize that chromosomal association of XIST RNA may initiate subsequent developmental events required to enact transcriptional silencing.
Abbreviations used in this paper: 5azadC, 5-azadeoxycytidine; rt, room temperature; RT, reverse transcription; Xa, active X chromosome; Xa-XIST+, reactivated X; Xi, inactive X chromosome; XIST/Xist, human/ mouse Xi-specific transcript.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Mercer, T. R., Dinger, M. E., Sunkin, S. M., Mehler, M. F., Mattick, J. S.
(2008). Specific expression of long noncoding RNAs in the mouse brain. Proc. Natl. Acad. Sci. USA
105: 716-721
[Abstract]
[Full Text]
-
Savarese, F., Flahndorfer, K., Jaenisch, R., Busslinger, M., Wutz, A.
(2006). Hematopoietic precursor cells transiently reestablish permissiveness for x inactivation.. Mol. Cell. Biol.
26: 7167-7177
[Abstract]
[Full Text]
-
Heard, E., Disteche, C. M.
(2006). Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev.
20: 1848-1867
[Abstract]
[Full Text]
-
Shumaker, D. K., Dechat, T., Kohlmaier, A., Adam, S. A., Bozovsky, M. R., Erdos, M. R., Eriksson, M., Goldman, A. E., Khuon, S., Collins, F. S., Jenuwein, T., Goldman, R. D.
(2006). From the Cover: Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc. Natl. Acad. Sci. USA
103: 8703-8708
[Abstract]
[Full Text]
-
Clemson, C. M., Hall, L. L., Byron, M., McNeil, J., Lawrence, J. B.
(2006). The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences. Proc. Natl. Acad. Sci. USA
103: 7688-7693
[Abstract]
[Full Text]
-
De Bonis, M.L., Cerase, A., Matarazzo, M.R., Ferraro, M., Strazzullo, M., Hansen, R.S., Chiurazzi, P., Neri, G., D'Esposito, M.
(2006). Maintenance of X- and Y-inactivation of the pseudoautosomal (PAR2) gene SPRY3 is independent from DNA methylation and associated to multiple layers of epigenetic modifications. Hum Mol Genet
15: 1123-1132
[Abstract]
[Full Text]
-
HEARD, E., CHAUMEIL, J., MASUI, O., OKAMOTO, I.
(2004). Mammalian X-Chromosome Inactivation: An Epigenetics Paradigm. Cold Spring Harb Symp Quant Biol
69: 89-102
[Abstract]
-
Sharp, A. J., Spotswood, H. T., Robinson, D. O., Turner, B. M., Jacobs, P. A.
(2002). Molecular and cytogenetic analysis of the spreading of X inactivation in X;autosome translocations. Hum Mol Genet
11: 3145-3156
[Abstract]
[Full Text]
-
Hall, L. L., Clemson, C. M., Byron, M., Wydner, K., Lawrence, J. B.
(2002). Unbalanced X;autosome translocations provide evidence for sequence specificity in the association of XIST RNA with chromatin. Hum Mol Genet
11: 3157-3165
[Abstract]
[Full Text]
-
Hall, L. L., Byron, M., Sakai, K., Carrel, L., Willard, H. F., Lawrence, J. B.
(2002). An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells. Proc. Natl. Acad. Sci. USA
99: 8677-8682
[Abstract]
[Full Text]
-
Morey, C., Arnaud, D., Avner, P., Clerc, P.
(2001). Tsix-mediated repression of Xist accumulation is not sufficient for normal random X inactivation. Hum Mol Genet
10: 1403-1411
[Abstract]
[Full Text]
-
Csankovszki, G., Nagy, A., Jaenisch, R.
(2001). Synergism of Xist Rna, DNA Methylation, and Histone Hypoacetylation in Maintaining X Chromosome Inactivation. JCB
153: 773-784
[Abstract]
[Full Text]
-
Hansen, R. S., Stoger, R., Wijmenga, C., Stanek, A. M., Canfield, T. K., Luo, P., Matarazzo, M. R., D'Esposito, M., Feil, R., Gimelli, G., Weemaes, C. M.R., Laird, C. D., Gartler, S. M.
(2000). Escape from gene silencing in ICF syndrome: evidence for advanced replication time as a major determinant. Hum Mol Genet
9: 2575-2587
[Abstract]
[Full Text]
-
Carrel, L., Cottle, A. A., Goglin, K. C., Willard, H. F.
(1999). From the Cover: A first-generation X-inactivation profile of the human X chromosome. Proc. Natl. Acad. Sci. USA
96: 14440-14444
[Abstract]
[Full Text]
-
Carrel, L., Willard, H. F.
(1999). Heterogeneous gene expression from the inactive X chromosome: An X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others. Proc. Natl. Acad. Sci. USA
96: 7364-7369
[Abstract]
[Full Text]
-
Heard, E., Mongelard, F., Arnaud, D., Chureau, C., Vourc'h, C., Avner, P.
(1999). Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells. Proc. Natl. Acad. Sci. USA
96: 6841-6846
[Abstract]
[Full Text]