The relationship between position and expression of genes on the kangarooXchromosome suggests a tissue-specific spread of inactivation from a single control site

Summary In marsupials,Xchromosome inactivation is paternal and incomplete. The tissue-specific pattern of inactivation ofX-linked loci (G6PD, PGK, GLA) has been attributed to a piecemeal inactivation of different regions of theX. We here propose an alternative hypothesis, in which inactivation of the marsupialXis a chromosome-wide event, but is differentially regulated in different tissues. This hypothesis was suggested by the relationship between the positions and activity of genes on the kangaroo paternalX. In the absence of an HPRT polymorphism, we have used somatic cell hybridization to assess the activity of the paternal HPRT allele in lymphocytes and fibroblasts. The absence of the paternalX, and of the paternal forms of G6PD or PGK, from 33 cell hybrids made by fusing HPRT-deficient rodent cells with lymphocytes or fibroblasts of heterozygous females, suggests that the HPRT gene on the paternalXis inactive in both tissues and therefore not selectable. Since HPRT is located medially on theXqnear GLA, which shares the same characteristics of activity, we suggest that the locus-specific and tissue-specific patterns of activity result from a differential spread of inactivation from a single control locus, located near HPRT and GLA, outwards in both directions to G6PD and PGK. The nucleolus organizer region on the short arm does not seem to be part of the inactivated unit.