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Identification of Trophoblast-Specific Regulatory Elements in the Mouse Placental Lactogen II Gene

Department of Biochemistry, Molecular Biology, and Cell Biology Northwestern University Evanston, Illinois 60208

Placental lactogen II, the major ligand for the PRL receptor during the second half of gestation in rodents, is synthesized specifically by placental trophoblast giant cells. A transient transgenic analysis has been used to localize the giant cell-specific regulatory region within the mouse placental lactogen II gene to sequences between -1340 and -2019 upstream of the transcriptional start site. More precise mapping of the regulatory elements has been accomplished by transfection of promoter constructs into Rcho-1 trophoblast cells, resulting in the characterization of two positive regulatory elements in the -1471 to -1340 region; two other regulatory elements have been implicated but not further characterized, a negative regulatory element between -2019 and -1778 and another positive element within the region from -1340 to -569. Both of the characterized positive regulatory elements are recognized by factors that are enriched in differentiated giant cells compared with proliferative trophoblasts, and these factors are either absent or at low levels in fibroblasts. The complexes that form on the two elements are distinct and neither element competes with the other for factor binding, thus implicating at least two different regulatory elements in late-gestational trophoblast giant cell-specific gene expression.

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