Transcriptional activation of the decidual/trophoblast prolactin-related protein gene.
The decidual/trophoblast PRL-related protein (d/tPRP) is dually expressed by decidual and trophoblast cells during pregnancy. We have characterized the proximal d/tPRP promoter responsible for directing d/tPRP expression in decidual and trophoblast cells. We have demonstrated that the proximal 93 bp of d/tPRP 5'-flanking DNA are sufficient to direct luciferase gene expression in primary decidual and Rcho-1 trophoblast cells, but not in fibroblast, undifferentiated uterine stromal cells or trophoblast cells of a labyrinthine lineage. The 93-bp d/tPRP promoter was also sufficient to direct differentiation-dependent expression in trophoblast giant cells. Mutational analysis demonstrated the differential importance of activating protein-1 and Ets regulatory elements (located within the proximal 93 bp of d/tPRP 5'-flanking 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 approximately 80% trophoblast cells. Disruption of the Ets regulatory element reduced d/tPRP promoter activity by approximately 50% in decidual cells, while inactivating the d/tPRP promoter in trophoblast cells. Protein interactions with the trophoblast Ets regulatory element were shown to be cell type specific and to change during trophoblast giant cell formation. In conclusion, a 93-bp region of the d/tPRP promoter is shown to contain regulatory elements sufficient for gene activation in decidual and trophoblast cells.
Orwig
K E
KE
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Soares
M J
MJ
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D004252:DNA Mutational Analysis; D003656:Decidua / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D015533:Transcriptional Activation / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D009687:Nuclear Proteins; C079559:Prl8a2 protein, rat; D011388:Prolactin