Tissue-specific promoters regulate aromatase cytochrome P450 expression.
In the human, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory has indicated that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start-site. This promoter is not utilized in placenta but instead, the promoter used to drive aromatase expression in placenta is at least 40 kb upstream from the translational start-site. In addition, there is a minor promoter used in the expression of a small proportion of placental transcripts which is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues including placenta-related cells such as JEG-3 choriocarcinoma cells, hydatidiform moles, and other fetal tissues such as fetal liver. On the other hand, in adipose tissue expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5'-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start-site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical.
Simpson
E R
ER
Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics/Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9051.
Mahendroo
M S
MS
Means
G D
GD
Kilgore
M W
MW
Corbin
C J
CJ
Mendelson
C R
CR
D000595:Amino Acid Sequence; D000818:Animals; D001141:Aromatase / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D010053:Ovary / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid
D001141:Aromatase