X chromosome

About: X chromosome is a research topic. Over the lifetime, 9862 publications have been published within this topic receiving 407354 citations. The topic is also known as: GO:0000805 & chrX.

Methylation of the mouse hprt gene differs on the active and inactive X chromosomes.

Abstract: It has been proposed that DNA methylation is involved in the mechanism of X inactivation, the process by which equivalence of levels of X-linked gene products is achieved in female (XX) and male (XY) mammals. In this study, Southern blots of female and male DNA digested with methylation-sensitive restriction endonucleases and hybridized to various portions of the cloned mouse hprt gene were compared, and sites within the mouse hprt gene were identified that are differentially methylated in female and male cells. The extent to which these sites are methylated when carried on the active and inactive X chromosomes was directly determined in a similar analysis of DNA from clonal cell lines established from a female embryo derived from a mating of two species of mouse, Mus musculus and Mus caroli. The results revealed two regions of differential methylation in the mouse hprt gene. One region, in the first intron of the gene, includes four sites that are completely unmethylated when carried on the active X and extensively methylated when carried on the inactive X. These same sites are extensively demethylated in hprt genes reactivated either spontaneously or after 5-azacytidine treatment. The second region includes several sites in the 3' 20kilobases of the gene extending from exon 3 to exon 9 that show the converse pattern; i.e., they are completely methylated when carried on the active X and completely unmethylated when carried on the inactive X. At least one of these sites does not become methylated after reactivation of the gene. The results of this study, together with the results of previous studies by others of the human hprt gene, indicate that these regions of differential methylation on the active and inactive X are conserved between mammalian species. Furthermore, the data described here are consistent with the idea that at least the sites in the 5' region of the gene play a role in the X inactivation phenomenon and regulation of expression of the mouse hprt gene.

LINE-1 elements and X chromosome inactivation: A function for “junk” DNA?

Abstract: X chromosome inactivation (XCI) is the mechanism used in mammals for dosage compensation of X-linked genes between chromosomally XX females and XY males. One of the two X chromosomes of females becomes transcriptionally inactive in every cell of the early embryo and remains so in all somatic cells throughout life. The phenomenon is highly unusual among mechanisms of gene regulation in that the whole, or almost the whole, of a chromosome is silenced. Most gene-silencing mechanisms, such as the position effect variegation system of Drosophila, operate over much shorter distances (1–2 megabases in that case). XCI is initiated from an X inactivation center on the X chromosome, and from there, it spreads throughout the chromosome. Segments of X chromosome without a center, through deletion or translocation, remain active. Conversely, if autosomal segments are attached to the X chromosome by translocation, the inactivating signal can spread for long distances into the autosome, up to 100 megabases in a recently described case (1). However, spread into autosomal material extends less far and is less effective in gene silencing than in the X chromosome itself (1–3). Recently, there have been great advances in knowledge of the X inactivation center. The Xist gene (Xist in mouse and XIST in human), located at the center, is expressed from the inactive X chromosome (Xi) and is necessary in cis for X inactivation. It encodes a nontranslated RNA. Before the onset of XCI in the embryo, Xist RNA is transcribed but is unstable. At the time of XCI, it becomes stable and accumulates. It then remains close to the Xi and spreads to coat the whole chromosome (reviewed in refs. 4 and 5). When Xist is introduced as a transgene into an autosome, its RNA will also coat the autosome, although less efficiently than …

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis

Abstract: Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immune-mediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease.