A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice.
In female mammals, up-regulation of Xist triggers X-chromosome inactivation in cis. Up-regulation is inhibited by sequences 3' to Xist contained within the antisense locus, Tsix. Inhibition could depend on transcription of Tsix and/or on DNA elements therein. Here we test the role of Tsix transcription by augmenting the duration and strength of Tsix expression. We find that Tsix hypertranscription is sufficient to block Xist RNA accumulation in a cis-limited manner. We propose that Tsix transcription is necessary to restrict Xist activity on the future active X and, conversely, that Tsix repression is required for Xist RNA accumulation on the future inactive X. We also find that Tsix hypertranscription does not affect X-chromosome choice. Thus, choice is mediated by elements within Tsix that are independent of promoter activity.
Stavropoulos
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Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Lu
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Lee
J T
JT
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D017931:DNA Primers; D020648:Peptide Elongation Factor 1; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; D012313:RNA