Transcription of the human transferrin gene in neuronal cells.

We have recently shown that a combination of three transcription factors governs the expression of the human transferrin gene in different brain cell types, oligodendrocytes, choroid plexus cells and neuronal cells. It was essential to elucidate the role of each factor in the regulation of transferrin gene transcription. Site-directed mutagenesis and co-transfection experiments in neuronal cells revealed that chicken ovalbumin upstream promoter transcription factor (COUP-TF), which binds to the promoter region I, acts as a repressor. Overexpression of the CCAAT/enhancer binding protein (C/EBP-alpha), which binds to the promoter region II, transactivates the -164/+1 promoter, even enables the -125/+1 region to promote transcription, and synergistically activates transcription in the presence of CREB. The C/EBP-alpha-mediated activation is antagonized by COUP-TF. The positive action of the cAMP response element-binding protein called CRI-BP is revealed by mutations of the central region I site which repress transcription. Moreover addition of dibutyryl cyclic AMP or overexpression of the catalytic subunit of protein kinase A increase transcription from the wild-type and not from the CRI mutant promoter, which shows that CRI-BP is responsible for mediating cAMP stimulation of Tf gene transcription.