Expression of genes from the human active and inactive X chromosomes

X-chromosome inactivation results in the cis-limited inactivation of many, but not all, of the genes on one of the pair of X chromosomes in mammalian females. In addition to the genes from the pseudoautosomal region, which have long been anticipated to escape inactivation, genes from several other regions of the human X chromosome have now been shown to escape inactivation and to be expressed from both the active and inactive X chromosomes. The growing number of genes escaping inactivation emphasizes the need for a reliable system for assessing the inactivation status of X-linked genes. Since many features of the active or inactive X chromosome, including transcriptional activity, are maintained in rodent/human somatic-cell hybrids, such hybrids have been used to study the inactivation process and to determine the inactivation status of human X-linked genes. In order to assess the fidelity of inactivation status in such hybrids, we have examined the expression of 33 X-linked genes in eight mouse/human somatic-cell hybrids that contain either the human active (three hybrids) or inactive X (five hybrids) chromosome. Inactivation of nine of these genes had previously been demonstrated biochemically in human cells, and the expression of these genes only in hybrids retaining an active X, but not in those retaining an inactive X, confirms that expression in hybrids reflects expression in human cells. Although the majority of genes tested showed consistent patterns of expression among the active X hybrids or inactive X hybrids, surprisingly, 5 of the 33 genes showed heterogeneous expression among the hybrids, demonstrating a significantly higher rate of variability than previously reported for other genes in either human somatic cells or mouse/human somatic-cell hybrids. These data suggest that at least some X-linked genes may be under additional levels of epigenetic regulation not previously recognized and that somatic-cell hybrids may provide a useful approach for studying these chromosomal phenomena.