produce them. In particular, the possible role of an 
X chromosome-unique, dispersed, moderately re- 
petitive element is being studied. Furthermore, this 
laboratory is attempting to determine whether 
these deletions occur more commonly in male or 
female germ cells and whether they arise preferen- 
tially during meiosis or during mitotic division of 
primordial germ cells. An effort to reproduce these 
^deletions in the cultured somatic cell system is also 
under way. 
III. Steroid Sulfatase Biosynthesis, Processing, and 
Regulation. 
STS is a ubiquitously distributed enzyme. Recent 
data from the cloning of several other sulfatases 
show that STS is part of a multigene family. How- 
ever, while most of the other sulfatases are local- 
ized in lysosomes, STS is not thought to reside in 
this cellular compartment. In situ hybridization, 
immunocytochemistry and immunoelectron mi- 
croscopy have been used to study the sites of syn- 
thesis and the localization of STS, which is predom- 
inantly found on the rough endoplasmic reticulum 
(RER). Manipulation of suitable expression con- 
structs and studies of post-translational processing 
should clarify those structural features that direct 
STS to the RER and not to the lysosome. Further- 
more, insight may be gained with regard to the 
pathogenesis of a new autosomal recessive human 
inherited condition, multiple sulfatase deficiency 
PUBLICATIONS 
disease. In this condition, activities of many of the 
different sulfatase enzymes are coordinately re- 
duced, probably through a mechanism that en- 
hances the rate of turnover of these proteins. 
Finally, the signals that abruptly cause STS trans- 
cription to begin after differentiation of placental cy- 
totrophoblast cells into syncytial trophoblast cells 
are being explored in a cell culture model. 
IV Regulation of X-encoded Gene Expression. 
An additional area of interest in the laboratory is 
the regulation of gene expression via X chromo- 
some inactivation. Several years ago. Dr. Shapiro's 
laboratory showed that X inactivation involves DNA 
methylation and that there are several genes that 
escape inactivation in a position-independent man- 
ner. The structure and function of promoters that 
are subject to X inactivation are being compared 
with those that are not so regulated to see if differ- 
ences in expression can be ascribed to this region. 
In addition, the role of DNA-binding proteins in the 
X-inactivation process is being studied by looking 
for the induction of new sequence-specific factors 
after differentiation of teratocarcinoma cells in 
vitro. The effect of methylation on the binding of 
such proteins is also being evaluated. 
Dr. Shapiro is also Professor of Pediatrics and Bi- 
ological Chemistry at the University of California 
School of Medicine at Los Angeles. 
Books and Chapters of Books 
Shapiro, L.J. 1989. Steroid sulfatase deficiency. In We Metabolic Basis of Inherited Disease (Scriver, C.R., 
Beaudet, A.L. , Sly WS., and Valle, P. , Eds.). New York: McGraw-Hill, pp 1945-1964. 
Articles 
Bergner, E.A., and Shapiro, L.J. 1988. Metabolism of ^H-dehydroepiandrosterone sulphate by subjects with 
steroid sulphatase deficiency. J Inherited Met ab Dis 11:403-415. 
Hsai, YE., Ford, C.A., Shapiro, L.J. , Hunt, J.A., and Ching, N.S.R 1989- Molecular screening for haemoglobin 
Constant Spring. Lancet 1:988-991. 
Lau, E.C., Mohandas, T.K., Shapiro, L.J., Slavkin, H.C., and Snead, M.L. 1989- Human and mouse amelogenin 
gene loci are on the sex chromosomes. Genomics 4:162-168. 
Mohandas, T.K., Passage, M.B., Williams, J.W, III, Sparkes, R.S., Yen, PH., and Shapiro, L.J. 1989. X-chromo- 
some inactivation in cultured cells from human chorionic villi. Som CellMol Genet 15:131-136. 
Salido, E.C., Yen, PH., Shapiro, L.J., Fisher, D.A., and Barajas, L. 1988. In situ hybridization of nerve growth 
factor mRNA in the mouse submandibular gland. Lab Invest 59:625-630. 
Salido, E.C., Yen, PH., Shapiro, L.J., Fisher, D.A., and Barajas, L. 1989. In situ hybridization of prepro-epider- 
mal growth factor mRNA in the mouse kidney. Am J Physiol 256:F632-F638. 
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