The human arylsulfatase-C isoenzymes: two distinct genes that escape from X inactivation.
Arylsulfatase C is a microsomal membrane-bound enzyme previously thought to be the same as steroid sulfatase, the only X-linked enzyme known to escape from X inactivation in man. We had shown that arylsulfatase C actually consists of two biochemically distinct isozymes, s and f. Only the s form has steroid sulfatase activity. The f and s forms were thought to be related through posttranslational or posttranscriptional modification of the same gene product. In part consistent with this hypothesis, we now report that in a panel of 28 rodent-human somatic cell hybrids, expression of both s and f was concordant only with the human X chromosome, thus showing that the f form is also X linked. In three separate somatic hybrids containing human X chromosomes in an inactive state, the f form was still expressed. Thus, similar to the s form, the f form also escapes from X inactivation. However, contrary to expectations, the s and f forms were not related by posttranslational modification of the same gene product. A full-length cDNA for the s form failed to hybridize to transcripts produced from an f-expressing cell line, showing that there is little sequence identity between the two. They are also not related by differential splicing of a common primary transcript, since fibroblasts from some patients with steroid sulfatase deficiency due to gene deletion of the s form continue to express the f form. Therefore, although the f and s isozymes of arylsulfatase C are X linked and escape from X inactivation, they are products from separate genes, thus providing a unique isoenzyme system to study possible gene duplication and regulation in the part of the human X chromosome that escapes inactivation.
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
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Shows
D000818:Animals; D001192:Arylsulfatases / Q000235:genetics*; D015152:Blotting, Northern; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004303:Dosage Compensation, Genetic; D005347:Fibroblasts; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D006822:Hybrid Cells; D007057:Ichthyosis / Q000201:enzymology / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D012313:RNA / Q000235:genetics; D043266:Steryl-Sulfatase; D013429:Sulfatases / Q000235:genetics*; D014960:X Chromosome
D015342:DNA Probes; D007527:Isoenzymes; D012313:RNA; D004247:DNA; D013429:Sulfatases; D001192:Arylsulfatases; D043266:Steryl-Sulfatase