Demonstration of tissue-specific promoters in nonprimate species that express aromatase P450 in placentae.
Abstract: Conversion of androgens to estrogens is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). Regulation of tissue-specific expression of P450arom in humans is due, in part, to alternative transcriptional start sites that arise as a consequence of the use of granulosa cells and placental tissue from cows, horses, and pigs (ungulates) in order to determine whether these species, like the human, utilize tissue-specific promoters to drive P450arom expression. The majority of transcripts in the placenta have 5'-termini that differ from those in the ovary upstream of a common site of divergence, indicative of a splice junction. The use of tissue-specific promoters by the bovine CYP19 gene would produce these results, as it does in the case of the human CYP19 gene. A bovine genomic library was then screened with probes that hybridize to ovary- or placenta-specific transcripts. Two clones of approximately 15 kb each in length were isolated; one hybridized with the ovary-specific sequence and the other hybridized with the placenta-specific sequence. Whereas the former sequence was contiguous with the downstream sequence containing the translational start site, the latter was identical only with the sequence of the placental transcripts upstream of the putative splice junction, indicating that this was the distal sequence. Bovine and human ovary-specific genomic sequences share 77% bp identity, while bovine and human placenta-specific sequences demonstrated only 39% bp identity. These results mirror those obtained in comparisons of human, bovine, equine, and porcine ovarian and placental RACE cDNA 5'-termini.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1995-11-01 PubMed ID: 8527520DOI: 10.1095/biolreprod53.5.1151Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research study explores the presence of tissue-specific promoters in non-primate species, specifically cows, horses, and pigs, which express aromatase P450, an enzyme involved in estrogen synthesis, in their placentas. The study’s methodology emphasizes analyzing the variation between transcripts in the placenta and ovary, revealing that like humans, these non-primate species also utilize tissue-specific promoters to govern P450arom expression.
Methodology
- Scientists examined placental tissue and granulosa cells from cows, horses, and pigs— referred to as ungulates—to determine whether these species used tissue-specific promoters to drive the expression of P450arom, akin to humans.
- They analyzed the structure of the transcripts generated, noting a majority of placental transcripts featured 5′-termini that were different from those in the ovary.
- The disparity between the transcripts alluded to the utilization of tissue-specific promoters by the bovine CYP19 gene, mirroring the function in the human CYP19 gene.
- To corroborate their findings, researchers screened a bovine genomic library using probes that would bind to ovary- or placenta-specific transcripts. This yielded two clones of approximately 15 kilobases each, one for each tissue type.
Results
- The sequence that merged with the ovary-specific clone was synonymous with the downstream sequence, encompassing the translational start site.
- Conversely, the placental sequence aligned only with the transcription of placental sequences before the alleged splice junction, signaling this as the furthest sequence.
- Comparative analysis of the bovine and human genomic sequences showed a 77% base pair (bp) identity for ovary-specific sequences, and a considerably lower match of 39% bp identity for placenta-specific sequences.
- The similarity between results obtained from analyzing human, bovine, equine, and porcine ovarian and placental RACE cDNA 5′-termini affirmed these observations.
Implications
- The study deepens our understanding of the mechanisms governing hormonal regulation and expression across species.
- Findings also help shape future research directions in comparative genomic studies concerning hormonal regulation and reproduction, opening avenues for further investigations into species-specific differences and potential clinical applications.
Cite This Article
APA
Hinshelwood MM, Liu Z, Conley AJ, Simpson ER.
(1995).
Demonstration of tissue-specific promoters in nonprimate species that express aromatase P450 in placentae.
Biol Reprod, 53(5), 1151-1159.
https://doi.org/10.1095/biolreprod53.5.1151 Publication
Researcher Affiliations
- Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Biochemistry and Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9051, USA.
MeSH Terms
- Animals
- Aromatase / genetics
- Base Sequence
- Cattle
- DNA, Complementary / chemistry
- DNA, Complementary / isolation & purification
- Exons
- Female
- Gene Expression
- Gene Library
- Granulosa Cells / chemistry
- Granulosa Cells / enzymology
- Horses
- Humans
- Molecular Sequence Data
- Placenta / chemistry
- Placenta / enzymology
- Pregnancy
- Promoter Regions, Genetic
- Sequence Homology
- Swine
Grant Funding
- 5-R01 HD13234 / NICHD NIH HHS
- 5-T32 HD07190 / NICHD NIH HHS
Citations
This article has been cited 5 times.- Vanselow J, Conley AJ, Corbin CJ, Berger T. Genomic Structure of the Porcine CYP19 Locus and Expression of the CYP19A3 Paralog.. Genes (Basel) 2021 Apr 6;12(4).
- Shah KB, Tripathy S, Suganthi H, Rudraiah M. Profiling of luteal transcriptome during prostaglandin F2-alpha treatment in buffalo cows: analysis of signaling pathways associated with luteolysis.. PLoS One 2014;9(8):e104127.
- Conley AJ, Corbin CJ, Hughes AL. Adaptive evolution of mammalian aromatases: lessons from Suiformes.. J Exp Zool A Ecol Genet Physiol 2009 Jun 1;311(5):346-57.
- Corbin CJ, Hughes AL, Heffelfinger JR, Berger T, Waltzek TB, Roser JF, Santos TC, Miglino MA, Oliveira MF, Braga FC, Meirelles FV, Conley AJ. Evolution of suiform aromatases: ancestral duplication with conservation of tissue-specific expression in the collared peccary (Pecari tayassu).. J Mol Evol 2007 Oct;65(4):403-12.
- Kamat A, Graves KH, Smith ME, Richardson JA, Mendelson CR. A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice.. Proc Natl Acad Sci U S A 1999 Apr 13;96(8):4575-80.
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