Crucial role of antisense transcription across theXistpromoter inTsix-mediatedXistchromatin modification

Ohhata, Tatsuya; Hoki, Yuko; Sasaki, Hidetada; Sado, Takashi

doi:10.1242/dev.008490

Cited by 123 publications

(114 citation statements)

References 29 publications

(43 reference statements)

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“…Extensive studies on Tsix in mouse embryos and ES cells with genetic manipulations have demonstrated that Tsix is a negative regulator of Xist and its expression prevents the upregulation of Xist on the same X chromosome by facilitating the formation of a repressive chromatin configuration at the Xist promoter (Lee & Lu 1999, Lee 2000, Sado et al 2001, Navarro et al 2005. Although it is not clear which of the RNA products or the action of antisense transcription is critical for its function, transcription across the Xist promoter appears to be crucial for Tsix to exert its negative effects on Xist (Ohhata et al 2008). At the onset of X-inactivation, the downregulation of Tsix on one X allows the differential upregulation of Xist in cis and induces subsequent inactivation of the X, whereas continued expression of Tsix on the other X prevents the upregulation of Xist and keeps the X active.…”

Section: X-linked Lncrnas That Coat An X Chromosomementioning

confidence: 99%

Species-specific differences in X chromosome inactivation in mammals

Sado

Sakaguchi

2013

Reproduction

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In female mammals, the dosage difference in X-linked genes between XX females and XY males is compensated for by inactivating one of the two X chromosomes during early development. Since the discovery of the X inactive-specific transcript (XIST) gene in humans and its subsequent isolation of the mouse homolog, Xist, in the early 1990s, the molecular basis of X chromosome inactivation (X-inactivation) has been more fully elucidated using genetically manipulated mouse embryos and embryonic stem cells. Studies on X-inactivation in other mammals, although limited when compared with those in the mice, have revealed that, while their inactive X chromosome shares many features with those in the mice, there are marked differences in not only some epigenetic modifications of the inactive X chromosome but also when and how X-inactivation is initiated during early embryonic development. Such differences raise the issue about what extent of the molecular basis of X-inactivation in the mice is commonly shared among others. Recognizing similarities and differences in X-inactivation among mammals may provide further insight into our understanding of not only the evolutionary but also the molecular aspects for the mechanism of X-inactivation. Here, we reviewed species-specific differences in X-inactivation and discussed what these differences may reveal.

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Section: X-linked Lncrnas That Coat An X Chromosomementioning

confidence: 99%

Species-specific differences in X chromosome inactivation in mammals

Sado

Sakaguchi

2013

Reproduction

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“…We previously showed that transcription overlapping the Xist promoter region is necessary for Tsix function (Ohhata et al 2008). Furthermore, several studies have shown that the endogenous Tsix promoter can be substituted for a constitutive or a tetracycline-responsive (Tet) promoter (Luikenhuis et al 2001;Stavropoulos et al 2001).…”

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confidence: 99%

“…Furthermore, several studies have shown that the endogenous Tsix promoter can be substituted for a constitutive or a tetracycline-responsive (Tet) promoter (Luikenhuis et al 2001;Stavropoulos et al 2001). Recruitment of DNA methylation and histone modifications such as H3K27me3 around the Xist promoter by Tsix have been reported in differentiated ES cells (Navarro et al 2006;Nesterova et al 2008), embryos (Sado et al 2005), and visceral endoderm (Ohhata et al 2008). Interactions of Tsix RNA with the DNA methyltransferase Dnmt3a (Sun et al 2006) and the PRC2 protein Ezh2 (Zhao et al 2008) have been reported with implications for the mechanism of Tsix-mediated recruitment of these modifications on the Xist promoter.…”

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confidence: 99%

Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in mice

Ohhata¹,

Senner²,

Hemberger³

et al. 2011

Genes Dev.

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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.

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“…Xist INV was generated from Xist Ex4del by a targeted inversion disrupting conserved sequences beginning 6 kb into exon 1 and extending to intron 5. Xist IVS was originally generated for the study of Tsix-mediated antisense regulation of Xist by Ohhata et al [41]. It contains an exogenously introduced 1 kb intron at 0.9 kb from the major transcription start site.…”

Section: Functional Domains Of Xist Rnamentioning

confidence: 99%

Advances in understanding chromosome silencing by the long non-coding RNA Xist

Sado

Brockdorff

2013

Phil. Trans. R. Soc. B

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In female mammals, one of the two X chromosomes becomes genetically silenced to compensate for dosage imbalance of X-linked genes between XX females and XY males. X chromosome inactivation (X-inactivation) is a classical model for epigenetic gene regulation in mammals and has been studied for half a century. In the last two decades, efforts have been focused on the X inactive-specific transcript ( Xist ) locus, discovered to be the master regulator of X-inactivation. The Xist gene produces a non-coding RNA that functions as the primary switch for X-inactivation, coating the X chromosome from which it is transcribed in cis . Significant progress has been made towards understanding how Xist is regulated at the onset of X-inactivation, but our understanding of the molecular basis of silencing mediated by Xist RNA has progressed more slowly. A picture has, however, begun to emerge, and new tools and resources hold out the promise of further advances to come. Here, we provide an overview of the current state of our knowledge, what is known about Xist RNA and how it may trigger chromosome silencing.

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Crucial role of antisense transcription across theXistpromoter inTsix-mediatedXistchromatin modification

Cited by 123 publications

References 29 publications

Species-specific differences in X chromosome inactivation in mammals

Species-specific differences in X chromosome inactivation in mammals

Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in mice

Advances in understanding chromosome silencing by the long non-coding RNA Xist

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