Differential expression of steroid sulphatase locus on active and inactive human X chromosome

Abstract

The X chromosome in mammalian somatic cells is subject to unique regulation--usually genes on a single X chromosome are expressed while those on other X chromosomes are inactivated. The X-locus for steroid sulphatase (STS; EC 3.1.6.2), the microsomal enzyme that catalyses the hydrolysis of various 3 beta-hydroxysteroid sulphates, is exceptional because it seems to escape inactivation. Evidence for this comes from fibroblast clones in females heterozygous for mutations that result in a severe deficiency of this enzyme in affected males; all clones from these heterozygotes have STS activity, and enzyme-deficient clones that are expected if the locus were subject to inactivation, have not been found. Further evidence that the STS locus escapes inactivation is that the human inactive X chromosomes contributes STS activity to mouse-human hybrid cells. On the basis of these hybrid studies the STS locus has been mapped to the distal half of the short arm (p22-pter) of the human X chromosome. Although the STS locus on both X chromosomes in human female cells is expressed, quantitative measurements of STS activity in males and females do not accurately reflect the sex differences in number of X chromosomes (Table 1). The ratio of mean values for normal females to that of normal males is greater than 1:1 but less than the ratio of 2:1 expected if STS loci on all X chromosomes were equally expressed. The incomplete dosage effect suggests that the STS locus on the inactive X chromosome might not be fully expressed. To test this hypothesis, we examine two heterozygotes for X-linked STS deficiency who were also heterozygous for the common electrophoretic variants of glucose-6-phosphate dehydrogenase (G6PD A and B). Studies of fibroblast clones from these females provide evidence, presented here, for differential expression of STS loci on the active and inactive X chromosome.

Long-range restriction map of the terminal part of the short arm of the human X chromosome.

“…This has been shown for MIC2, the only pseudoautosomal gene identified at present (2). Two chromosome X-specific genes (XG encoding the Xg blood group and STS encoding steroid sulfatase), mapping to Xp22.3, also escape, at least partially, this inactivation (3)(4)(5). By analogy, it has been suggested that such X-specific genes from Xp22.3, which are at least partially insensitive to X-inactivation, are remnants of an ancestral pseudoautosomal region that once extended more proximally on Xp22.3.…”

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

“…This segment is of considerable interest because in this region, a reduction of X inactivation has been observed (Mohandas et al 1979;Miiller et al 1980;Migeon et al 1982). Furthermore, this region is thought to be involved in crossover events with the distal end of the short arm of the Y chromosome (de la Chapelle 1981;Polani 1982;Burgoyne 1982).…”

Sex chromosome evolution: platypus gene mapping suggests that part of the human X chromosome was originally autosomal.

“…escape inactivation (32)(33)(34)(35)(36) suggest that the process is still Ipials was initially exincomplete in some regions of the human X chromosome, am the ancestral maiperhaps because these genes lack sequences that respond to aller marsupial X chroa signal spreading from an X inactivation center. The obserriabsence also from the vation that some genes that escape inactivation in humans are ficult to explain on this inactivated in mouse suggests that the inactivation system verged earlier from the may be more completely evolved in mouse (31 …”