Initiation of X chromosome inactivation requires the presence, in cis, of the X 
inactivation center (XIC). The Xist gene, which lies within the XIC region in 
both human and mouse and has the unique property of being expressed only from 
the inactive X chromosome in female somatic cells, is known to be essential for 
X inactivation based on targeted deletions in the mouse. Although our 
understanding of the developmental regulation and function of the mouse Xist 
gene has progressed rapidly, less is known about its human homolog. To address 
this and to assess the cross-species conservation of X inactivation, a 480-kb 
yeast artificial chromosome containing the human XIST gene was introduced into 
mouse embryonic stem (ES) cells. The human XIST transcript was expressed and 
could coat the mouse autosome from which it was transcribed, indicating that the 
factors required for cis association are conserved in mouse ES cells. Cis 
inactivation as a result of human XIST expression was found in only a proportion 
of differentiated cells, suggesting that the events downstream of XIST RNA 
coating that culminate in stable inactivation may require species-specific 
factors. Human XIST RNA appears to coat mouse autosomes in ES cells before in 
vitro differentiation, in contrast to the behavior of the mouse Xist gene in 
undifferentiated ES cells, where an unstable transcript and no chromosome 
coating are found. This may not only reflect important species differences in 
Xist regulation but also provides evidence that factors implicated in Xist RNA 
chromosome coating may already be present in undifferentiated ES cells.