XIST HAS PROPERTIES OF THE X-CHROMOSOME INACTIVATION CENTER

X-chromosome inactivation is the process by which female mammals (with two X chromosomes) achieve expression of X-chromosomal genes equivale nt to that of males (one X and one Y chromosome)(1,2). This results in the transcriptional silencing of virtually all genes on one of the X chromosomes in female somatic cells, X-chromosome inactivation has bee n shown to act in cis and to initiate and spread from a single site on the X chromosome known as the X-inactivation centre (Xic)(2,3). The X ic has been localized to a 450-kilobase region of the mouse X chromoso me(4). The Xist gene also maps to this region and is expressed exclusi vely from the inactive X chromosome(3-7). Xist is unusual in that it a ppears not to code for a protein but produces a nuclear RNA which colo calizes with the inactive X chromosome(4,8). The creation of a null al lele of Xist in embryonic stem cells has demonstrated that this gene i s required for X inactivation to occur in cis(9). Here we show that Xi st, introduced onto an autosome, is sufficient by itself far inactivat ion in cis and that Xist RNA becomes localized close to the autosome i nto which the gene is integrated. In addition, the presence of autosom al Xist copies leads to activation of the endogeneous Xist gene in som e cells, suggesting that elements required for some aspects of chromos ome counting are contained within the construct, Thus the Xist gene ex hibits properties of the X-inactivation centre.