XCE HAPLOTYPES SHOW MODIFIED METHYLATION IN A REGION OF THE ACTIVE X-CHROMOSOME LYING 3' TO XIST

During early mammalian embryogenesis, one of the two X chromosomes in somatic cells of the female becomes inactivated through a process that is thought to depend on a unique initiator region, the X-chromosome i nactivation center (Xic). The recently characterized Xist sequence (X- inactive-specific transcript) is thought to be a possible candidate fo r Xic. In mice a further genetic element, the X chromosome-controlling element (Xce), is also known to influence the choice of which of the two X chromosomes is inactivated. We report that a region of the mouse X chromosome lying 15 kb distal to Xist contains several sites that s how hypermethylation specifically associated with the active X chromos ome. Analysis of this region in various Xce strains has revealed a cor relation between the strength of the Xce allele carried and the methyl ation status of this region. We propose that such a region could be in volved in the initial stages of the inactivation process and in partic ular in the choice of which of the two X chromosomes present in a fema le cell will be inactivated.