<i>Tsix</i>defective in splicing is competent to establish<i>Xist</i>silencing

Sado, Takashi; Hoki, Yuko; Sasaki, Hidetada

doi:10.1242/dev.02670

Cited by 43 publications

(34 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During embryogenesis, methylation marks are first laid down on previously unmethylated DNA by the de novo methyltransferases Dnmt3a and -3b, and are later perpetuated through DNA replication by the maintenance methyltransferase Dnmt1. One way by which Tsix might function to repress Xist is to recruit Dnmt3a activity to methylate and silence the Xist promoter (Sado et al 2006;Sun et al 2006). Similarly, Kcnq1ot1 may recruit Dnmt1 (Mohammad et al 2010).…”

Section: Mechanisms Of Action: Finding Pattern In Chaosmentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

show abstract

Section: Mechanisms Of Action: Finding Pattern In Chaosmentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

View full text Add to dashboard Cite

show abstract

“…Of the 464 colonies picked up, 11 harbored the expected homologous recombination (Xist CAG2L ). Chimeric males were crossed with females heterozygous for the Tsix-deficient X (XX ΔTsix ) (Sado et al, 2001) to facilitate the transmission of Xp carrying the Xist CAG2L allele (X CAG2L ) to female offspring as previously shown (Hoki et al, 2009;Ohhata et al, 2008;Sado et al, 2005Sado et al, , 2006. Females thus generated (X ΔTsix X…”

Section: Cagmentioning

confidence: 99%

A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects

et al. 2015

Self Cite

View full text Add to dashboard Cite

The dosage difference of X-linked genes between the sexes in mammals is compensated for by genetic inactivation of one of the X chromosomes in XX females. A noncoding RNA transcribed from the Xist gene at the onset of X chromosome inactivation coats the X chromosome in cis and induces chromosome-wide heterochromatinization. Here, we report a new Xist allele (Xist CAG ) driven by a CAG promoter, which is known to be constitutively active in many types of cells. The paternal transmission of Xist CAG resulted in the preferential inactivation of the targeted paternal X (Xp) not only in the extra-embryonic but also the embryonic lineage, whereas maternal transmission ended with embryonic lethality at the early postimplantation stage with a phenotype that resembled mutant embryos carrying a maternal deficiency in Tsix, an antisense negative regulator of Xist, in both sexes. Interestingly, we found that the upregulation of Xist CAG in preimplantation embryos temporally differed depending on its parental origin: its expression started at the 4-to 8-cell stages when paternally inherited, and Xist CAG was upregulated at the blastocyst stage when maternally inherited. This might indicate that the Xist locus on Xp is permissive to transcription, but the Xist locus on the maternal X (Xm) is not. We extrapolated from these findings that the maternal Xist allele might manifest a chromatin structure inaccessible by transcription factors relative to the paternal allele. This might underlie the mechanism for the maternal repression of Xist at the early cleavage stage when Tsix expression has not yet occurred on Xm.

show abstract

“…Real-time PCR was carried out as previously described (Sado et al, 2006), using Xist2281F and Xist 2424R as primers for Xist, Tsix2F and P422R for Tsix, and GapdF and GapdR2 for Gapd. The expression levels of Xist and Tsix were normalized to Gapd levels as previously described (Sado et al, 2006).…”

Section: Rt-pcrmentioning

confidence: 99%

“…We previously demonstrated, however, that this female-specific lethality is sometimes rescued by the simultaneous presence of a Tsix deficiency on the maternal X (Ohhata et al, 2008;Sado et al, 2005;Sado et al, 2006). Accordingly, the male chimeras were crossed with females heterozygous for the Tsix deficient allele (ΔTsix) (Sado et al, 2001) to facilitate transmission of…”

Section: δA2loxmentioning

confidence: 99%

A proximal conserved repeat in theXistgene is essential as a genomic element for X-inactivation in mouse

et al. 2009

Self Cite

View full text Add to dashboard Cite

X-inactivation in female mammals is triggered by the association of non-coding Xist RNA in cis with the X chromosome. Although it has been suggested that the A-repeat located in the proximal part of the Xist RNA is required for chromosomal silencing in ES cells, its role in mouse has not yet been addressed. Here, we deleted the A-repeat in mouse and studied its effects on X-inactivation during embryogenesis. The deletion, when paternally transmitted, caused a failure of imprinted X-inactivation in the extraembryonic tissues, demonstrating the essential role of the A-repeat in X-inactivation in the mouse embryo. Unexpectedly, the failure of X-inactivation was caused by a lack of Xist RNA rather than by a defect in the silencing function of the mutated RNA, which we expected to be expressed from the mutated X. Interestingly, the normally silent paternal copy of Tsix, which is an antisense negative regulator of Xist, was ectopically activated in the preimplantation embryo. Furthermore, CpG sites in the promoter region of paternal Xist, which are essentially unmethylated in the extraembryonic tissues of the wild-type female embryo, acquire a significant level of methylation on the mutated paternal X. These findings demonstrate that the DNA sequence deleted on the mutated X, most probably the A-repeat, is essential as a genomic element for the appropriate transcriptional regulation of the Xist/Tsix loci and subsequent X-inactivation in the mouse embryo.

show abstract

Tsixdefective in splicing is competent to establishXistsilencing

Cited by 43 publications

References 30 publications

Long Noncoding RNAs: Past, Present, and Future

Long Noncoding RNAs: Past, Present, and Future

A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects

A proximal conserved repeat in theXistgene is essential as a genomic element for X-inactivation in mouse

Contact Info

Product

Resources

About