Structure of human estrogen and aryl sulfotransferase gene. Two mRNA species issued from a single gene.

Abstract

Estrone sulfate is the predominant form of estrogens found in the circulation in women and could thus serve as precursor for active estrogens in target tissues by removal of the sulfate group through the action of endogenous steroid sulfatase. Recently, we isolated a cDNA encoding human placental estrogen sulfotransferase that differs from brain aryl sulfotransferase only in the 5'-noncoding sequence. To increase our knowledge of the regulation and tissue-specific expression of sulfotransferase gene, we screened a lambda EMBL3 library of human leucocyte genomic DNA using the estrogen sulfotransferase cDNA as probe and isolated a clone containing almost the whole gene sequence. Sequencing of the gene indicates that it is included in approximately 7.7 kilobases and contains nine short exons separated by eight introns. The two first exons, named exon 1a and exon 1b, are noncoding and correspond to the 5'-untranslated sequences of human brain and human placental estrogen sulfotransferase cDNAs, respectively. Transfection of chloramphenicol acetyltransferase reporter gene vectors containing the 5'-flanking sequence upstream from exon 1a and exon 1b in human adrenal adenocarcinoma cells indicates that both sequences possess promoter activity. The present results thus indicate that brain aryl sulfotransferase and placental human placental estrogen sulfotransferase mRNA species are transcribed from a single gene by alternate exon 1a and exon 1b promoters, respectively. Using DNA from panels of human/rodent somatic cell hybrids and amplification of the gene by polymerase chain reaction, the human placental estrogen sulfotransferase gene was assigned to chromosome 16.