Transcription of genes encoding pregnancy-specific glycoproteins is regulated by negative promoter-selective elements

The human pregnancy-specific glycoprotein (PSG) genes comprise a family of 11 highly conserved members whose expression is maximal in placental cells and marginal in other cell types. We have investigated here the molecular b asis of PSG regulation by analysing a large regulatory region of the PSG-5 gene in cells that do and do not express these genes. The promoter region ( -254 to -43), which does not contain a TATA-box, large GC-rich sequences or a classical initiator, was active in all cell types analysed. Additional u pstream sequences up to position -3204 repressed promoter activity. Two ind ependent repressor regions were identified and found to operate effectively in HeLa, COS-7 and HTR8/SVneo placental cells. More significantly, these n egatively acting modules failed to repress a heterologous TATA-containing t hymidine kinase promoter. Detailed transcriptional and DNA-protein analyses of the proximal repressor region (-605 to -254) revealed the presence of b oth negative and positive cis-acting elements. Disruption of the repressive functions resulted in an enhanced transcription of the reporter constructs . In conclusion, these results demonstrate that PSG-5 gene transcription is highly repressed by promoter-selective negative regulatory regions and the relief of repression allows enhanced PSG-5 gene transcription irrespective of the cell type. Furthermore, our findings suggest that PSG genes are exp ressed mainly through a derepression mechanism.