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Science 29 July 2005:
Vol. 309. no. 5735, pp. 768 - 771
DOI: 10.1126/science.1113673
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Reports

Regulation of X-Chromosome Counting by Tsix and Xite Sequences

Jeannie T. Lee*

In mammals, X-inactivation establishes X-chromosome dosage parity between males and females. How X-chromosome counting regulates this process remains elusive, because neither the hypothesized inactivation "blocking factor" nor the required cis-elements have been defined. Here, a mouse knockout and transgenic analysis identified DNA sequences within the noncoding Tsix and Xite genes as numerators. Homozygous deficiency of Tsix resulted in "chaotic choice" and a variable number of inactive X's, whereas overdosage of Tsix/Xite inhibited X-inactivation. Thus, counting was affected by specific Tsix/Xite mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. The mutations affect XX and XY cells differently, demonstrating that counting and choice are regulated not by one "blocking factor," but by both a "blocking" and a "competence" factor.

Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School Boston, MA 02114, USA.

* E-mail: lee{at}molbio.mgh.harvard.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Intersection of the RNA Interference and X-Inactivation Pathways.
Y. Ogawa, B. K. Sun, and J. T. Lee (2008)
Science 320, 1336-1341
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X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells.
S. S. Silva, R. K. Rowntree, S. Mekhoubad, and J. T. Lee (2008)
PNAS 105, 4820-4825
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Sensing X Chromosome Pairs Before X Inactivation via a Novel X-Pairing Region of the Xic.
S. Augui, G. J. Filion, S. Huart, E. Nora, M. Guggiari, M. Maresca, A. F. Stewart, and E. Heard (2007)
Science 318, 1632-1636
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Dynamics and interplay of nuclear architecture, genome organization, and gene expression.
R. Schneider and R. Grosschedl (2007)
Genes & Dev. 21, 3027-3043
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Dosage compensation in mammals: fine-tuning the expression of the X chromosome.
E. Heard and C. M. Disteche (2006)
Genes & Dev. 20, 1848-1867
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Mapping of DNA Replication Origins to Noncoding Genes of the X-Inactivation Center.
R. K. Rowntree and J. T. Lee (2006)
Mol. Cell. Biol. 26, 3707-3717
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An essential role for the DXPas34 tandem repeat and Tsix transcription in the counting process of X chromosome inactivation.
S. Vigneau, S. Augui, P. Navarro, P. Avner, and P. Clerc (2006)
PNAS 103, 7390-7395
   Abstract »    Full Text »    PDF »
Differential Methylation of Xite and CTCF Sites in Tsix Mirrors the Pattern of X-Inactivation Choice in Mice..
R. M. Boumil, Y. Ogawa, B. K. Sun, K. D. Huynh, and J. T. Lee (2006)
Mol. Cell. Biol. 26, 2109-2117
   Abstract »    Full Text »    PDF »
Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation.
N. Xu, C.-L. Tsai, and J. T. Lee (2006)
Science 311, 1149-1152
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)