title: Tsix defective in splicing is competent to establish Xist silencing.
abstract: 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.
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima, 411-8540, Japan. tsado@lab.nig.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sado
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hoki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics; D034622:RNA Interference; D012326:RNA Splicing; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics; D049951:X Chromosome Inactivation
chemical_list: D002843:Chromatin; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA; D012313:RNA