A 450-KB TRANSGENE DISPLAYS PROPERTIES OF THE MAMMALIAN X-INACTIVATION CENTER

X inactivation results in inactivation of one X chromosome to compensa te for gene dosage differences between mammalian females and males. It requires the X-inactivation center (Xic) and Xist in cis. We report t hat introducing 450 kb of murine Xic/Xist sequences onto autosomes act ivates female dosage compensation in male ES cells. Xist is induced up on differentiation and can be expressed from both endogenous and ectop ic loci, suggesting that elements for counting and choosing Xs are pre sent in the transgene. Differentiating transgenic ES cells undergo exc essive cell death. Postnatally, Xist is expressed only from the transg ene. Ectopic Xist RNA structurally associates with the autosome and ma y inactivate a marker gene in cis. These results argue that the Xic is contained within 450 kb and that these sequences are sufficient for c hromosome counting, choosing, and initiation of X inactivation.