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Molecular and Cellular Biology, April 2005, p. 2757-2769, Vol. 25, No. 7
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.7.2757-2769.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identification of Developmentally Specific Enhancers for Tsix in the Regulation of X Chromosome Inactivation

Nicholas Stavropoulos,1,2,3 Rebecca K. Rowntree,1,2,3 and Jeannie T. Lee1,2,3*

Howard Hughes Medical Institute,1 Department of Molecular Biology, Massachusetts General Hospital,2 Department of Genetics, Harvard Medical School, Boston, Massachusetts3

Received 4 November 2004/ Returned for modification 14 December 2004/ Accepted 21 December 2004

X chromosome inactivation silences one of two X chromosomes in the mammalian female cell and is controlled by a binary switch that involves interactions between Xist and Tsix, a sense-antisense pair of noncoding genes. On the future active X chromosome, Tsix expression suppresses Xist upregulation, while on the future inactive X chromosome, Tsix repression is required for Xist-mediated chromosome silencing. Thus, understanding the binary switch mechanism depends on ascertaining how Tsix expression is regulated. Here we have taken an unbiased approach toward identifying Tsix regulatory elements within the X chromosome inactivation center. First, we defined the major Tsix promoter and found that it cannot fully recapitulate the developmental dynamics of Tsix expression, indicating a requirement for additional regulatory elements. We then delineated two enhancers, one classical enhancer mapping upstream of Tsix and a bipartite enhancer that flanks the major Tsix promoter. These experiments revealed the intergenic transcription element Xite as an enhancer of Tsix and the repeat element DXPas34 as a component of the bipartite enhancer. Each enhancer contains DNase I-hypersensitive sites and appears to confer developmental specificity to Tsix expression. Characterization of these enhancers will facilitate the identification of trans-acting regulatory factors for X chromosome counting and choice.

* Corresponding author. Mailing address: Department of Genetics, Harvard Medical School, Wellman 913, 50 Blossom St., Boston, MA 02114. Phone: (617) 726-5943. Fax: (617) 726-6893. E-mail: lee{at}molbio.mgh.harvard.edu.

Molecular and Cellular Biology, April 2005, p. 2757-2769, Vol. 25, No. 7
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.7.2757-2769.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lee, J. T. (2009). Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev. 23: 1831-1842 [Abstract] [Full Text]  
  • Starmer, J., Magnuson, T. (2009). A new model for random X chromosome inactivation. Development 136: 1-10 [Abstract] [Full Text]  
  • Navarro, P., Page, D. R., Avner, P., Rougeulle, C. (2006). Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program.. Genes Dev. 20: 2787-2792 [Abstract] [Full Text]  
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  • ANGUERA, M.C., SUN, B.K., XU, N., LEE, J.T. (2006). X-Chromosome Kiss and Tell: How the Xs Go Their Separate Ways. Cold Spring Harb Symp Quant Biol 71: 429-437 [Abstract]  
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