A 500-bp region, approximate to 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice

In humans, aromatase P450 (product of CYP19 gene), which catalyzes conversi on of C-19 steroids to estrogens, is expressed in a number of tissues, incl uding ovary, adipose, and syncytiotrophoblast of the placenta, The 5' untra nslated regions of CYP19 mRNA transcripts in these tissues are encoded by d ifferent tissue-specific first exons, which are spliced onto a common site just upstream of the translation initiation site in exon II. In placenta, t he 5' untranslated region of CYP19 mRNA transcripts is encoded by exon I.1, which lies approximate to 40 kb upstream of exon II. To map genomic sequen ces required for placenta-specific CYP19 expression, fusion genes containin g 2,400 and 501 bp of placenta-specific exon I.1 5' flanking DNA linked to the human growth hormone gene (hGH), as reporter, were introduced into tran sgenic mice. Expression of CYP19(I.1):hGH fusion genes containing as little as 501 bp of 5' flanking DNA was placenta-specific and developmentally reg ulated. Furthermore, transgene expression occurred specifically in the laby rinthine trophoblast of the mouse placenta, which contains syncytial cells that may be analogous to the human syncytiotrophoblast. We show that a rela tively small segment of DNA ( approximate to 500 bp) >40 kb upstream of the protein coding region of a human gene is able to direct expression in an a ppropriate tissue- and cell-specific manner in transgenic mice. These findi ngs suggest that 5' flanking DNA within 501 bp of exon I.1 of the human CYP 19 gene contains cis-acting elements that bind placenta-specific transcript ion factors that are conserved between humans and mice.