Cd. Scatena et S. Adler, TRANS-ACTING FACTORS DICTATE THE SPECIES-SPECIFIC PLACENTAL EXPRESSION OF CORTICOTROPIN-RELEASING FACTOR GENES IN CHORIOCARCINOMA CELL-LINES, Endocrinology, 137(7), 1996, pp. 3000-3008
CRF, in addition to its role in the hypothalamus, demonstrates species
-specific expression in the placentas of higher primates, but not rode
nts. Transient transfections of BeWo and JEG-3 choriocarcinoma cells,
as models for human trophoblasts, demonstrate regulated expression of
human (h) CRF-luciferase reporter genes, whereas little or no expressi
on is detected in other lines, including CV-1 cells. The rodent chorio
carcinoma cell line, Rcho-1, a model for rodent trophoblasts, is defec
tive in the expression of transfected hCRF genes. The mouse CRF promot
er behaves similarly to the corresponding hCRF construct. It is active
in BeWo and inactive in Rcho-1 cells. The transcriptional response to
cAMP contributes to the specific expression of CRF. Analyses of delet
ed or mutated hCRF promoters identify a key role for protein kinase A-
dependent pathways. A major part, but not all, of this effect is media
ted by the canonical cAMP response element conserved in mouse, rat, an
d human CRF promoters. Additional deletions of the human CRF promoter
identify control regions that also contribute to the observed species-
specific expression pattern, and each identified region binds factors
in nuclear extracts derived from the appropriate cell line. These stud
ies using human and rodent choriocarcinoma cell lines as models of pla
cental trophoblasts demonstrate dominant effects of cellular trans-act
ing factors, rather than DNA sequence differences, in dictating the sp
ecies-specific placental expression of CRF.