This results in mosaicism for X-linked traits in heterozygous females (Lyon, 1961). (1993) noted that primary X inactivation in tissues of the embryo proper is typically random, so that in approximately 50% of cells the paternal X is inactive, while in the others the maternal-derived X chromosome is inactive. X inactivation is a form of dosage compensation occurring in mammals, leading to the reduction of the effective X chromosome dosage of most X-linked genes in XX females to that pertaining in XY males. (2006) proposed that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing. Thus, Tsix and Xite function both in cis and in trans. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Pairing occurs transiently at the onset of X inactivation and is specific to the X inactivation center. (2006) showed that in mouse embryonic stem cells interchromosomal pairing mediates communication between X chromosomes to regulate X inactivation and ensure mutually exclusive silencing. The mutations affected XX and XY mouse cells differently, demonstrating that counting and choice are regulated not by one blocking factor, but by both a blocking and a competence factor. Thus, counting was affected by specific Tsix/Xite mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. Homozygous deficiency of Tsix resulted in 'chaotic choice' and a variable number of inactive X's, whereas overdosage of Tsix/Xite inhibited X inactivation. Lee (2005) used mouse knockout and transgenic analysis to identify DNA sequences within the noncoding Tsix and Xite genes as numerators of the X chromosome. Therefore, Xite is a candidate for the Xce, the classical modifier of XCI ratios. Ogawa and Lee (2003) proposed that allele-specific Xite action promotes Tsix asymmetry and generates X chromosome inequality. Xite is located 20 to 32 kb downstream of Xist. Truncating Xite RNA was inconsequential, indicating that Xite action does not require intact transcripts. At the onset of X-chromosome inactivation (XCI), deleting Xite downregulated Tsix in cis and skewed XCI ratios, suggesting that Xite promotes Tsix persistence on the active X. Xite harbors intergenic transcription start sites and DNase I hypersensitive sites with allelic differences.
They named this cis element 'X inactivation intergenic transcription element,' or Xite. Ogawa and Lee (2003) discovered a cis element in the mouse X inactivation center that regulates Tsix ( 300181).
The precise nature of Xce in the mouse and of its presumed homolog in human was not known. Thus, Xce in the mouse and its presumed homolog in human is distinct from Xist. Using this valuable source of polymorphism, they obtained results that, while indicating the tight linkage of Xist to Xce, suggested that Xce localizes outside the 170-kb region immediately surrounding Xist, delineated by 2 of the new markers described by them. (1993) set out to map Xce more precisely, specifically in relation to Xist, by the isolation of new microsatellite markers deriving from this region. As an alternative approach to elucidate the role of Xist, Simmler et al. When the Xist sequence ( 314670) was identified lying within the candidate interval for Xic and Xce in both human and mouse, it was suggested by Ballabio and Willard (1992) that Xist may itself be Xic. There is also evidence for the existence of a locus on the mouse X chromosome, the X chromosome-controlling element Xce, capable in some way of controlling X inactivation. Cytologic and genetic analysis of cells carrying rearranged X chromosomes has provided evidence both in human and mouse that the process of X inactivation is under control of a unique element, known as the X inactivation center XIC/Xic. This results in mosaicism for X-linked traits in heterozygous females ( Lyon, 1961).
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