Disease relevance of Xce

• To characterize the Xic further, we performed deletional analysis across the 450-kb region by yeast-artificial-chromosome fragmentation and phage P1 cloning [1].
• Hypersensitivity in the D-band equivalent region of the X chromosome does, however, exist, this site being early replicating in somatic cells and housing the X inactivation centre (Xce) [2].

High impact information on Xce

• In mammals, dosage compensation is achieved by X inactivation and is regulated in cis by the X-inactivation centre (Xic) and Xist [3].
• The Xic controls X-chromosome counting, choice of X to inactivate and initiation of silencing [3].
• Tsix RNA has no conserved ORFs, is seen exclusively in the nucleus and is localized at Xic [3].
• Xist maps within Xic (refs 7-10) and is necessary in cis for inactivation [4].
• These results argue that the Xic is contained within 450 kb and that these sequences are sufficient for chromosome counting, choosing, and initiation of X inactivation [5].

Biological context of Xce

• In mice a further genetic element, the X chromosome-controlling element (Xce), is also known to influence the choice of which of the two X chromosomes is inactivated [6].
• Analysis of this region in various Xce strains has revealed a correlation between the strength of the Xce allele carried and the methylation status of this region [6].
• Xce haplotypes show modified methylation in a region of the active X chromosome lying 3' to Xist [6].
• We did not identify any autosomal loci with significant associations and thus show conclusively that Xce is the only major locus to influence X inactivation patterns in the crosses analyzed [7].
• Subsequent analysis of recombinant chromosomes allowed for the establishment of a maximum 1.85-Mb candidate region for the Xce locus [7].

Anatomical context of Xce

• In addition to the relative activity of the PGK-1 allozymes, we also measured the absolute activity of PGK-1 in oocytes obtained from three types of Xce homozygous females.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• The work reported here was designed to elucidate whether the nonrandom inactivation of the imprinted XP in yolk-sac endoderm could be modified, or even overridden, by the effect of different Xce alleles [9].
• Using the modified Kanda method we have therefore studied the proportion of cells at metaphase with the XP inactive in separated yolk-sac endoderm and mesoderm of mouse embryos heterozygous for a marker X chromosome (Cattanach's translocation) carrying different Xce alleles on XP and XM [9].
• However, the influence of the Xce locus on the randomness of X-inactivation in embryos seems to operate also in ES cell lines [10].
• Imprinted XCI, normally found in preimplantation embryos and extraembryonic tissues, was not observed in blastocysts or placentae from later stage clones, although fetuses recapitulated the Xce effect [11].

Associations of Xce with chemical compounds

• Estrogen plays a significant role in regulating the mRNA levels of different Cgs/Sgs suggesting functional and regulatory differences in Cg/Sg proteins [12].
• Combined in situ hybridization and immunohistochemistry using rat pituitary revealed that the glycoprotein hormone-secreting cells expressed all three Cg/Sg mRNAs in approximately equal amounts [12].
• CCK(2) receptor antagonists containing the conformationally constrained phenylalanine derivatives, including the new amino acid Xic [13].

Other interactions of Xce

• The recently characterized Xist sequence (X-inactive-specific transcript) is thought to be a possible candidate for Xic [6].
• This finding also demonstrates that the timing of reactivation of maternal Pgk-1 is not influenced by the Xce locus [8].
• Critical control sequences in the Xic include the non-coding RNAs Xist and Tsix, and long-range chromatin elements [14].
• As Ta25H/+ females show the striped X-inactivation coat pattern, the putative X-inactivation centre, Xce, which lies close to Ta, cannot be located within the region deleted [15].
• Cloning and characterization of a murine brain specific gene Bpx and its human homologue lying within the Xic candidate region [16].

Analytical, diagnostic and therapeutic context of Xce

• Using the quantitative RT-PCR single nucleotide primer extension (SNuPE) assay, we found that the amount of Xist RNA in adult kidney of three mouse strains was less than approximately 2000 transcripts per cell, with only modest differences between strains carrying different Xce alleles [10].
• Transgenesis represents a stringent test for defining the minimal region that can carry out the functions attributed to the Xic [17].
• Xist, a gene mapping to the X-inactivation centre (Xic), is exclusively expressed from the inactive X-chromosome and is thought to be involved in the initiation of X-inactivation [18].
• To gain some insight into the regulation and possible functions of specific Cg/Sg members, female rats were ovariectomized for different periods with and without estrogen replacement and the pituitaries were subsequently analyzed by in situ hybridization and Northern hybridization analyses [12].

References