Characterization of a murine gene expressed from the inactive X chromosome

Abstract

In mammals, equal dosage of gene products encoded by the X chromosome in male and female cells is achieved by X inactivation. Although X-chromosome inactivation represents the most extensive example known of long range cis gene regulation, the mechanism by which thousands of genes on only one of a pair of identical chromosomes are turned off is poorly understood. We have recently identified a human gene (XIST) exclusively expressed from the inactive X chromosome. Here we report the isolation and characterization of its murine homologue (Xist) which localizes to the mouse X inactivation centre region and is the first murine gene found to be expressed from the inactive X chromosome. Nucleotide sequence analysis indicates that Xist may be associated with a protein product. The similar map positions and expression patterns for Xist in mouse and man suggest that this gene may have a role in X inactivation.

DNA hypomethylation can activate Xist expression and silence X-linked genes.

“…The Xist gene maps to the Xic (Borsani et al 1991;Brockdorff et al 1991) and is required in cis for X-inactivation (Penny et al 1996). Xist/XIST is transcribed solely from the Xi in female somatic cells (Borsani et al 1991;Brockdorff et al 1991;Brown et al 1991).…”

“…Xist/XIST is transcribed solely from the Xi in female somatic cells (Borsani et al 1991;Brockdorff et al 1991;Brown et al 1991). Activation of Xist expression precedes X-inactivation suggesting that Xist expression may initiate this process (Kay et al 1993).…”

Genomic Imprinting and Epigenetic Control of Development

“…In eutherians, XCI is in part regulated through a ncRNA, Xist, that coats the silent X chromosome (Xi) in cis ( Fig. 3) (Borsani et al 1991;Brockdorff et al 1991;Brown 1991;Brown et al 1991a;Clemson et al 1996). The Xist gene is indispensible for both imprinted and random XCI: X chromosomes with deletions of the Xist gene are never inactivated (Kay et al 1994;Penny et al 1996;Marahrens et al 1997).…”

Inactivation du chromosome X et pluripotence

“…Concernant l'inactivation du chromosome X, la découverte fondamentale du gène Xist en 1991 a représenté une avancée majeure dans le domaine [8,9]. Lié au chromosome X, le gène Xist produit un ARN non codant de grande taille possédant la propriété unique > L'inactivation d'un chromosome X (ICX) chez les femelles (XX) est le processus qui permet de compenser le niveau d'expression des gènes du chromosome X entre les mammifères mâles (XY) et femelles (XX) [1].…”