Evolution of placenta-specific gene expression: comparison of the equine and human gonadotropin alpha-subunit genes.
Primate and equine species are thought to be unique among mammals in synthesizing placental gonadotropin glycoprotein hormones. Human chorionic gonadotropin (CG) and equine pregnant mare's serum gonadotropin (PMSG) are produced in placenta by the specific activation of a glycoprotein hormone alpha-subunit gene and a corresponding beta-subunit gene. The evolutionary mechanisms for the apparently independent acquisition of tissue specificity were investigated by cloning the 5' flanking region of the equine alpha-subunit gene and comparing the DNA elements and trans-acting factors involved in placental expression. We find that though the equine gene is expressed and induced by cAMP, it does not contain the elements known to confer tissue-specific expression to the human gene, the cAMP response element (CRE) and the trophoblast-specific element (TSE), nor does it bind to the trans-acting factors CREB and TSEB. Instead, an additional factor (alpha-ACT) is found which binds to the equine and human, but not the murine, alpha-subunit genes in a region between the positions of the CRE and TSE and confers cAMP responsiveness.
Steger
D J
DJ
Salk Institute, La Jolla, California 92037.
Altschmied
J
J
Büscher
M
M
Mellon
P L
PL
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D002822:Choriocarcinoma; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics*; D006736:Horses / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015292:Glycoprotein Hormones, alpha Subunit; D000242:Cyclic AMP