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First published online 15 November 2006
doi: 10.1242/dev.02670

Development 133, 4925-4931 (2006)
Published by The Company of Biologists 2006
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Tsix defective in splicing is competent to establish Xist silencing

Takashi Sado1,2,3,*, Yuko Hoki1,3 and Hiroyuki Sasaki1,2

1 Division of Human Genetics, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima, 411-8540, Japan.
2 Department of Genetics, The Graduate University for Advanced Studies (Sokendai), 1111 Yata, Mishima, 411-8540, Japan.
3 PRESTO, Japan Science and Technology Agency (JST), 4-1-8, Honcho, Kawaguchi, Saitama, 332-0012, Japan.

* Author for correspondence (e-mail: tsado{at}lab.nig.ac.jp)

Accepted 3 October 2006

Dosage differences of X-linked genes between male and female mammals are compensated for by a mechanism known as X-inactivation, and the noncoding Xist gene plays a crucial role in this process. The expression of Xist is regulated in cis by its noncoding antisense gene, Tsix, whose transcripts (though a fraction of them stay unspliced), are processed like common proteincoding RNAs. It has been suggested that certain classes of sense-antisense pairs of RNA are causally involved in not only gene regulation but also higher order chromatin structure in various organisms. In fact, recent studies demonstrated that Tsix modulates Xist expression through modification of the chromatin structure. It is still unknown, however, whether the RNA product is important for the function of Tsix or whether the antisense transcription is sufficient. To obtain insight into this issue, we eliminated the splicing products of Tsix in the mouse and explored the effects of this elimination on Tsix-mediated Xist silencing. To our surprise, the Xist locus was stably repressed on the X carrying the splicing-defective Tsix allele. Moreover, the repressive chromatin configuration was properly established at the Xist locus. These unexpected results indicate that the splicing products are dispensable for Tsix-mediated Xist silencing.

Key words: X-inactivation, Antisense regulation, Xist, Tsix


Related articles in Development:

Splicing: the main brace for X-inactivation?

Development 2006 133: e2405. [Full Text]  



This article has been cited by other articles:


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T. Ohhata, Y. Hoki, H. Sasaki, and T. Sado
Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification
Development, January 15, 2008; 135(2): 227 - 235.
[Abstract] [Full Text] [PDF]


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