Far upstream sequences regulate the human prolactin promoter transcription

The human prolactin gene is mainly expressed in pituitary lactotrope cells, but transcription from an alternative, far upstream promoter was detected in lymphoid, placental and mammary cells. We describe the transcriptional a ctivity in rat pituitary cells of the complete region separating the two pr omoters, using transient transfection experiments. A far upstream activatin g region was only functional in combination with the prolactin promoter. DN aseI protection experiments revealed, in addition to binding sites for the pituitary-specific factor Pit-1, sites (e.g. SD1) for several ubiquitous fa ctors and one lymphoid-specific factor (SD4). A single copy of the ubiquito us site SD1 or the lymphoid-specific site SD4 was unable to activate transc ription of a heterologous promoter in pituitary cells. However, SD1 activat ed transcription in nonpituitary cells and SD4 was functional specifically in lymphoid cells. Five copies of a distal site (D8) activated transcriptio n in each cell type tested. Gel retardation experiments show that this site binds the specific factor C/EBP in liver and a distinct factor in other ce ll types. Our results suggest that different elements within this large reg ion direct specific expression from each promoter via a complex interplay b etween cell-specific and ubiquitous transcription factors, Copyright (C) 20 00 S. Karger AG, Basel.