Human XIST cDNAs containing at least 8 exons and totaling 17 kb were isolated and sequenced within the region on
the X chromosome known to contain the X inactivation center (Brown et al., 1992). The XIST gene includes several
tandem repeats, the most 5-prime of which are evolutionarily conserved. The gene does not contain any significant
conserved open reading frames (ORFs) and thus does not appear to encode a protein, suggesting that XIST may function
as a structural RNA within the nucleus.
NCBI Summary:
X inactivation is an early developmental process in mammalian females that transcriptionally silences one of the pair of X chromosomes, thus providing dosage equivalence between males and females. The process is regulated by several factors, including a region of chromosome X called the X inactivation center (XIC). The XIC comprises several non-coding and protein-coding genes, and this gene was the first non-coding gene identified within the XIC. This gene is expressed exclusively from the XIC of the inactive X chromosome, and is essential for the initiation and spread of X-inactivation. The transcript is a spliced RNA. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. Mutations in the XIST promoter cause familial skewed X inactivation. [provided by RefSeq, Apr 2012]
General function
Nucleic acid binding, DNA binding
Comment
The role of the Xist gene in X chromosome inactivation as the master regulatory switch locus was supported solely by
indirect evidence until the experiments of Penny et al. (1996), who provided direct evidence by gene targeting of Xist in
mouse embryonic stem (ES) cells. Their results provided evidence for the absolute requirement of Xist in the process of
X chromosome inactivation. When ES cells that are chromosomally XX are maintained in the undifferentiated state,
both X chromosomes remain active and Xist is expressed at very low levels; however, when they are allowed to
differentiate, X inactivation occurred and Xist expression increased markedly.
Cellular localization
Nuclear
Comment
Expression of serum lncRNA-Xist in patients with polycystic ovary syndrome and its relationship with pregnancy outcome. Liu M et al. (2020) Long non-coding RNA X-inactive specific transcript (LncRNA Xist) plays a pivotal role in various types of human diseases, while its involvement in polycystic ovary syndrome (PCOS) remains unknown. In the study we aimed to investigate if downregulate Xist expression is involved in PCOS and is correlated with adverse pregnant outcomes in PCOS. In this study, expression of lncRNA Xist in peripheral blood collected from both PCOS patients and controls were detected by qRT-PCR. Diagnostic values of Xist expression for PCOS were evaluated by ROC curve analysis. Correlation between Xist expression and pregnant outcomes of PCOS patients was analyzed. Compared with controls, Xist was significantly downregulated in patients with PCOS but not in patients with other types of diseases. Xist expression can be used to effectively distinguish PCOS patients from controls. Reduced expression level of Xist was significantly correlated with adverse pregnant outcomes of PCOS patients but not healthy controls. The downregulation of Xist expression may be involved in PCOS and is correlated with adverse pregnant outcomes in PCOS.//////////////////
Ovarian function
Follicle endowment, Early embryo development
Comment
Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries. Zhou M et al. (2021) The fecundity of female mammals is resolved by the limited size of the primordial follicle (PF) pool formed perinatally. The establishment of PF pool is accompanied by a significant programmed oocyte death. Long non-coding RNAs (lncRNA) are central modulators in regulating cell apoptosis or autophagy in multiple diseases, however, the significance of lncRNAs governing perinatal oocyte loss remains unknown. Here we find that Yin-Yang 1 (YY1) directly binds to the lncRNA X-inactive-specific transcript (Xist) promoter and facilitates Xist expression in the perinatal mouse ovaries. Xist is highly expressed in fetal ovaries and sharply downregulated along with the establishment of PF pool after birth. Gain or loss of function analysis reveals that Xist accelerates oocyte autophagy, mainly through binding to pre-miR-23b or pre-miR-29a in the nucleus and preventing the export of pre-miR-23b/pre-miR-29a to the cytoplasm, thus resulting in decreased mature of miR-23b-3p/miR-29a-3p expression and upregulation miR-23b-3p/miR-29a-3p co-target, STX17, which is essential for timely control of the degree of oocyte death in prenatal mouse ovaries. Overall, these findings identify Xist as a key non-protein factor that can control the biogenesis of miR-23b-3p/miR-29a-3p, and this YY1-Xist-miR-23b-3p/miR-29a-3p-STX17 regulatory axis is responsible for perinatal oocyte loss through autophagy.////////////////// RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos. Matoba S et al. Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient. Most SCNT-generated embryos die after implantation because of unidentified, complex epigenetic errors in the process of postimplantation embryonic development. Here we identify the most upstream level of dysfunction leading to impaired development of clones by using RNAi against Xist, a gene responsible for X chromosome inactivation (XCI). A prior injection of Xist-specific siRNA into reconstructed oocytes efficiently corrected SCNT-specific aberrant Xist expression at the morula stage, but failed to do so thereafter at the blastocyst stage. However, we found that shortly after implantation, this aberrant XCI status in cloned embryos had been corrected autonomously in both embryonic and extraembryonic tissues, probably through a newly established XCI control for postimplantation embryos. Embryo transfer experiments revealed that siRNA-treated embryos showed 10 times higher survival than controls as early as embryonic day 5.5 and this high survival persisted until term, resulting in a remarkable improvement in cloning efficiency (12% vs. 1% in controls). Importantly, unlike control clones, these Xist-siRNA clones at birth showed only a limited dysregulation of their gene expression, indicating that correction of Xist expression in preimplantation embryos had a long-term effect on their postnatal normality. Thus, contrary to the general assumption, our results suggest that the fate of cloned embryos is determined almost exclusively before implantation by their XCI status. Furthermore, our strategy provides a promising breakthrough for mammalian SCNT cloning, because RNAi treatment of oocytes is readily applicable to most mammal species.
Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Inoue K et al. Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight- to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Avner R, et al 2000
showed that Xist is expressed earlier in
development, in unfertilized mouse oocytes as well as in pronuclei stage
zygotes.
Follicle stages
Preovulatory
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment:Marahrens et al. (1997) generated male and female mice that
carried a deletion in the structural gene but maintained a functional Xist promoter. They found that males with the
mutated allele developed normally and were fertile. Females who inherited the mutant gene from their mothers
also developed normally, with the wildtype paternal X being exclusively inactivated in every cell. However,
female mice inheriting the mutant Xist allele on the paternal X chromosome were severely growth-retarded and
died early in embryogenesis. The wildtype maternal X chromosome was inactive in every cell of the
growth-retarded embryo proper, whereas both chromosomes were expressed in the mutant female trophoblast
where X inactivation is imprinted. However, an XO mouse with a paternally inherited Xist mutation was healthy
and appeared normal. They concluded that the imprinted lethal phenotype of the mutant females
was due to the inability of extraembryonic tissue with 2 active X chromosomes to sustain the embryo.