Nucleic Acids Research, 2000, Vol. 28, No. 4 1036-1043
© 2000 Oxford University Press
AP-2 family members regulate basal and cAMP-induced expression of human chorionic gonadotropin
The Departments of Reproductive Medicine and Neurosciences and the Center for the Study of Reproductive Biology and Disease, University of California at San Diego, La Jolla, CA 92093-0674, USA and 1The Salk Institute, La Jolla, CA 92037, USA
The AP-2 family of transcriptional regulator proteins has three members, 
, ß and 
. AP-2 and are expressed in placenta and in the human trophoblast cell line JEG-3. AP-2 has been shown to regulate expression of the placental human chorionic gonadotropin (hCG) - and ß-subunit genes, however, previous work did not distinguish between the family members. Tryptic peptides of the AP-2 protein complexes purified from JEG-3 cells by oligo-affinity chromatography using the hCG AP-2 site match the amino acid sequence of AP-2. The fact that AP-2 is present at significant levels and binds the hCG trophoblast-specific element suggests that AP-2 is at least part of the binding complex in vivo and plays a role in regulating hCG expression. We show that mutation of each of four AP-2 binding sites within the hCGß promoter decreases expression in transfection assays, demonstrating that all four sites are required for maximal expression in JEG-3 cells. Furthermore, we find differences in regulation of the family members: AP-2 mRNA levels increase in response to cAMP while AP-2 mRNA levels do not. The demonstrated importance of the AP-2 sites in controlling hCG and ß expression and the likely involvement of more than one family member suggest that a balance in AP-2 proteins is involved in coordinate regulation of these genes. Moreover, many placenta-restricted genes are regulated by AP-2 proteins, thus members of this family may play an important overall role in placenta-specific expression.
* To whom correspondence should be addressed at: Department of Reproductive Medicine 0674, 2057 CMM-E, University of California at San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0674, USA. Tel: +1 858 534 1312; Fax: +1 858 534 1438; Email: pmellon@ucsd.edu Present addresses: Cynthia LiCalsi, Dura Pharmaceuticals Inc., 7475 Lusk Boulevard, San Diego, CA 92121, USA David J. Steger, Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143-0448, USA Marita Buescher, IMCB, National University of Singapore, 10 Kent Ridge Crescent, 0511 Singapore, Republic of Singapore
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