Document Detail


Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in mice.
MedLine Citation:
PMID:  21852535     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The noncoding Tsix RNA is an antisense repressor of Xist and regulates X inactivation in mice. Tsix is essential for preventing the inactivation of the maternally inherited X chromosome in extraembryonic lineages where imprinted X-chromosome inactivation (XCI) occurs. Here we establish an inducible Tsix expression system for investigating Tsix function in development. We show that Tsix has a clear functional window in extraembryonic development. Within this window, Tsix can repress Xist, which is accompanied by DNA methylation of the Xist promoter. As a consequence of Xist repression, reactivation of the inactive X chromosome (Xi) is widely observed. In the parietal endoderm, Tsix represses Xist and causes reactivation of an Xi-linked GFP transgene throughout development, whereas Tsix progressively loses its Xist-repressing function from embryonic day 9.5 (E9.5) onward in trophoblast giant cells and spongiotrophoblast, suggesting that Tsix function depends on a lineage-specific environment. Our data also demonstrate that the maintenance of imprinted XCI requires Xist expression in specific extraembryonic tissues throughout development. This finding shows that reversible XCI is not exclusive to pluripotent cells, and that in some lineages cell differentiation is not accompanied by a stabilization of the Xi.
Authors:
Tatsuya Ohhata; Claire E Senner; Myriam Hemberger; Anton Wutz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  25     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-19     Completed Date:  2011-12-07     Revised Date:  2014-10-14    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1702-15     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Lineage / genetics
DNA Methylation
Embryo, Mammalian / cytology,  embryology,  metabolism
Female
Gene Expression Regulation, Developmental
Green Fluorescent Proteins / genetics,  metabolism
In Situ Hybridization, Fluorescence
Male
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence
Placenta / cytology,  embryology,  metabolism
Pregnancy
RNA, Long Noncoding
RNA, Untranslated / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Trophoblasts / metabolism
X Chromosome / genetics*
X Chromosome Inactivation / genetics*
Grant Support
ID/Acronym/Agency:
087530//Wellcome Trust; 087530/Z/08/A//Wellcome Trust; BBS/E/B/0000C230//Biotechnology and Biological Sciences Research Council; G0800784//Medical Research Council
Chemical
Reg. No./Substance:
0/RNA, Long Noncoding; 0/RNA, Untranslated; 0/Tsix transcript, mouse; 0/XIST non-coding RNA; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

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