STRUCTURE OF HUMAN ESTROGEN AND ARYL SULFOTRANSFERASE GENE - 2 MESSENGER-RNA SPECIES ISSUED FROM A SINGLE-GENE

Estrone sulfate is the predominant form of estrogens found in the circ ulation in women and could thus serve as precursor for active estrogen s in target tissues by removal of the sulfate group through the action of endogenous steroid sulfatase. Recently, we isolated a cDNA encodin g human placental estrogen sulfotransferase that differs fi om brain a ryl sulfotransferase only in the 5'-noncoding sequence. To increase ou r knowledge of the regulation and tissue-specific expression of the su lfotransferase gene, we screened a lambda EMBL3 Library of human leuco cyte genomic DNA using the estrogen sulfotransferase cDNA as probe and isolated a clone containing almost the whole gene sequence. Sequencin g of the gene indicates that it is included in approximately 7.7 kilob ases and contains nine short exons separated by eight introns. The two first exons, named exon la and exon Ib, are noncoding and correspond to the 5'-untranslated sequences of human brain and human placental es trogen sulfotransferase cDNAs, respectively. Transfection of chloramph enicol acetyltransferase reporter gene vectors containing the 5'-flank ing sequence upstream from exon la and exon Ib in human adrenal adenoc arcinoma cells indicates that both sequences possess promoter activity . The present results thus indicate that brain aryl sulfotransferase a nd placental human placental estrogen sulfotransferase mRNA species ar e transcribed from a single gene by alternate exon 1a and exon 1b prom oters, respectively. Using DNA from panels of human/rodent somatic cel l hybrids and amplification of the gene by polymerase chain reaction, the human placental estrogen sulfotransferase gene was assigned to chr omosome 16.