Disease relevance of XIST

• Here we investigate four adult male HT-1080 fibrosarcoma cell lines expressing ectopic human XIST and demonstrate that these postdifferentiation cells can undergo chromosomal inactivation outside of any normal developmental context [1].
• A previous study localized the breakpoints of two acquired isodicentric X chromosomes associated with myelodysplasia to a 450-kb region proximal to the XIST gene [2].
• Small ring (X) chromosomes lacking the XIST gene at Xq13.2 have been associated with a severe phenotype that includes mental retardation, facial dysmorphism and congenital abnormalities [3].
• Prune-belly syndrome and other anomalies in a stillborn fetus with a ring X chromosome lacking XIST [4].
• Detection of partially hypomethylated XIST alleles in prostate cancer tissues might be useful for the identification of cases with pronounced hypomethylation, which tend to be more aggressive [5].

Psychiatry related information on XIST

• Thus, the unusual phenotypic features and mental retardation associated with the presence of a r(X) cannot be explained solely on the basis of presence or absence of XIST [6].

High impact information on XIST

• BRCA1 supports XIST RNA concentration on the inactive X chromosome [7].
• A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation [8].
• X chromosome inactivation, XIST, and pursuit of the X-inactivation center [9].
• The gene does not contain any significant conserved ORFs and thus does not appear to encode a protein, suggesting that XIST may function as a structural RNA within the nucleus [10].
• The XIST gene includes several tandem repeats, the most 5' of which are evolutionarily conserved [10].

Biological context of XIST

• The localization of the XIST gene to the XIC region on the human X chromosome implicates XIST in some aspect of X inactivation [11].
• In males, neither methylation of FMR1 nor expression of XIST was detected, demonstrating that the duplicated chromosome was not subject to inactivation [12].
• The current study was designed to shed light on the question whether the multiple X chromosomes in testicular germ cell tumor are active or inactive through a complex mechanism of X chromosomal gain and XIST expression [13].
• Human XIST cDNAs containing at least eight exons and totaling 17 kb have been isolated and sequenced within the region on the X chromosome known to contain the X inactivation center [10].
• XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure [14].

Anatomical context of XIST

• The roles of supernumerical X chromosomes and XIST expression in testicular germ cell tumors [13].
• XIST RNA remains with the nuclear matrix fraction after removal of chromosomal DNA [14].
• As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia, nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active [15].
• The RNA is widely expressed in adult and fetal tissues and is found in the cytoplasmic fraction of human cells, which is also the case for the H19 non-translated RNA, but differs from the XIST RNA which is found predominantly in the nucleus [16].
• X-inactivation analysis for the methylation status of the AR gene indicated that, of eight cases with XIST-positive r(X) chromosomes in more than 10% (23%-62%) of lymphocytes (cases 5-12), cases 5-10 had selective X-inactivation, whereas cases 11 and 12 had active X disomy [17].

Associations of XIST with chemical compounds

• Here we report a rare cytosine to guanine mutation in the XIST minimal promoter that underlies both epigenetic and functional differences between the two X chromosomes in nine females from two unrelated families [8].
• We describe here another example of an XIST-expressing human-hamster hybrid that lacks X-linked gene repression in which the human XIST gene present on an active X chromosome was reactivated by treatment with 5-aza-2'-deoxycytidine [18].
• Therefore, we have analyzed methylation and expression of the XIST gene by bisulfite sequencing and real-time RT-PCR [5].

Other interactions of XIST

• Our findings indicate that the lack of XCI may be a frequent phenomenon in breast tumorigenesis, which occurs independently of BRCA1 status and XIST expression and is due to the loss of Xi and replication of Xa and not to the reactivation of the native Xi [19].
• Moreover, in one of the BRCA1wt cell line the restoring of XIST expression using a histone deacetylase inhibitor, did not lead to XCI [19].
• The inactive X (Xi) differs from its active homologue (Xa) in a number of ways, including increased methylation of CpG islands, replication late in S phase, underacetylation of histone H4 and association with XIST RNA [20].
• XIST Repression in the Absence of DNMT1 and DNMT3B [21].
• This pattern of transcriptional regulation of SYCP1 is similar to that observed for XIST in TGCTs [22].

Analytical, diagnostic and therapeutic context of XIST

• Consistent with this, fluorescence in situ hybridization experiments demonstrate localization of XIST RNA within the nucleus to a position indistinguishable from the X inactivation-associated Barr body [10].
• BRCA1, a breast and ovarian tumor suppressor, colocalizes with markers of the inactive X chromosome (Xi) on Xi in female somatic cells and associates with XIST RNA, as detected by chromatin immunoprecipitation [7].
• We have developed a methylation-sensitive polymerase chain reaction (MS-PCR) strategy that combines repeat-length and methylation analysis of the CGG-repeat and the promoters of the FMR1 and XIST genes [23].
• Results of FISH and RT-PCR experiments indicate that the XIST locus is missing in the ring X chromosome and not expressed [24].
• Using PCR, Southern blot analysis, and in situ hybridization, we have looked for the presence of the XIST locus in tiny ring X chromosomes from eight females who have multiple congenital malformations and severe mental retardation [25].

References