Transcriptional activation of the decidual/trophoblast prolactin-related protein gene

The decidual/trophoblast PRL-related protein (d/tPRP) is dually expressed b y decidual and trophoblast cells during pregnancy. We have characterized th e proximal d/tPRP promoter responsible for directing d/tPRP expression in d ecidual and trophoblast cells. We have demonstrated that the proximal 93 bp of d/tPRP 5'-flanking DNA are sufficient to direct luciferase gene express ion in primary decidual and Rcho-1 trophoblast cells, but not in fibroblast , undifferentiated uterine stromal cells or trophoblast cells of a labyrint hine lineage. The 93-bp d/tPRP promoter was also sufficient to direct diffe rentiation-dependent expression in trophoblast giant cells. Mutational anal ysis demonstrated the differential importance of activating protein-1 and E ts regulatory elements (located within the proximal 93 bp of d/tPRP 5'-flan king DNA) for activation of the d/tPRP promoter in decidual vs. trophoblast cells. Disruption of the activating protein-1 regulatory element inhibited d/tPRP promoter activity by more than 95% in decidual cells, and approxima tely 80% trophoblast cells. Disruption of the Ets regulatory element reduce d d/tPRP promoter activity by approximately 50% in decidual cells, while in activating the d/tPRP promoter in trophoblast cells. Protein interactions w ith the trophoblast Ets regulatory element were shown to be cell type speci fic and to change during trophoblast giant cell formation, In conclusion, a 93-bp region of the d/tPRP promoter is shown to contain regulatory element s sufficient for gene activation in decidual and trophoblast cells.