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Far upstream sequences regulate the human prolactin promoter transcription
C Van De Weerdt1, B Peers, A Belayew
1Laboratoire de Biologie Mol¿eculaire et de G¿enie G¿en¿etique, Universit¿e de Li¿ege, Institut de Chimie B6, Sart-Tilman, Belgique.
Neuroendocrinology
|February 25, 2000
Summary
Investigating the prolactin gene, this study reveals a large regulatory region controlling its expression. Different transcription factors interact to ensure cell-specific gene activity.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The human prolactin gene is primarily expressed in pituitary lactotrope cells.
- Alternative promoter usage has been observed in lymphoid, placental, and mammary cells.
Purpose of the Study:
- To characterize the transcriptional activity of the region between the two prolactin gene promoters in rat pituitary cells.
- To identify regulatory elements and transcription factors involved in cell-specific prolactin gene expression.
Main Methods:
- Transient transfection experiments were used to assess promoter activity.
- DNaseI protection and gel retardation assays identified transcription factor binding sites.
Main Results:
- A far upstream activating region required the prolactin promoter to function.
- Specific binding sites for pituitary-specific (Pit-1), ubiquitous, and lymphoid-specific factors were identified.
- The distal site D8 bound C/EBP in liver cells and other factors in different cell types, activating transcription across various cell lines.
Conclusions:
- A complex interplay between cell-specific and ubiquitous transcription factors within a large regulatory region governs prolactin gene expression from distinct promoters.
- Different elements within this region mediate cell-specific expression patterns.