EVIDENCE THAT RANDOM AND IMPRINTED XIST EXPRESSION IS CONTROLLED BY PREEMPTIVE METHYLATION

The mouse Xist gene is expressed exclusively from the inactive X chrom osome and may control the initiation of X inactivation. We show that i n somatic tissues the 5' end of the silent Xist allele on the active X chromosome is fully methylated, while the expressed allele on the ina ctive X is completely unmethylated. In tissues that undergo imprinted paternal Xist expression and imprinted X inactivation, the paternal Xi st allele is unmethylated, and the silent maternal allele is fully met hylated. In the male germline, a developmentally regulated demethylati on of Xist occurs at the onset of meiosis and is retained in mature sp ermatozoa. This may be the cause of imprinted expression of the patern al Xist allele. A role for methylation in the control of Xist expressi on is further supported by the finding that in differentiating embryon ic stem cells during the initiation of X inactivation, differential me thylation of Xist alleles precedes the onset of Xist expression.