A 500-bp region, approximately 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 conversion of C19 steroids to estrogens, is expressed in a number of tissues, including ovary, adipose, and syncytiotrophoblast of the placenta. The 5' untranslated regions of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are spliced onto a common site just upstream of the translation initiation site in exon II. In placenta, the 5' untranslated region of CYP19 mRNA transcripts is encoded by exon I.1, which lies approximately 40 kb upstream of exon II. To map genomic sequences required for placenta-specific CYP19 expression, fusion genes containing 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 transgenic mice. Expression of CYP19(I.1):hGH fusion genes containing as little as 501 bp of 5' flanking DNA was placenta-specific and developmentally regulated. Furthermore, transgene expression occurred specifically in the labyrinthine trophoblast of the mouse placenta, which contains syncytial cells that may be analogous to the human syncytiotrophoblast. We show that a relatively small segment of DNA (approximately 500 bp) >40 kb upstream of the protein coding region of a human gene is able to direct expression in an appropriate tissue- and cell-specific manner in transgenic mice. These findings suggest that 5' flanking DNA within 501 bp of exon I.1 of the human CYP19 gene contains cis-acting elements that bind placenta-specific transcription factors that are conserved between humans and mice.
Kamat
A
A
Department of Biochemistry, The Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center at Dallas, TX 75235-9038, USA.
Graves
K H
KH
Smith
M E
ME
Richardson
J A
JA
Mendelson
C R
CR
D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012727:Sex Characteristics; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone; D001141:Aromatase