TRANSCRIPTION OF THE HUMAN TRANSFERRIN GENE IN NEURONAL CELLS

We have recently shown that a combination of three transcription facto rs governs the expression of the human transferrin gene in different b rain cell types, oligodendrocytes, choroid plexus cells and neuronal c ells. It was essential to elucidate the role of each factor in the reg ulation of transferrin gene transcription. Site-directed mutagenesis a nd co-transfection experiments in neuronal cells revealed that chicken ovalbumin upstream promoter transcription factor (COUP-TF), which bin ds to the promoter region I, acts as a repressor. Overexpression of th e CCAAT/enhancer binding protein (C/EBP-alpha), which binds to the pro moter region II, transactivates the -164/+1 promoter, even enables the -125/+1 region to promote transcription, and synergistically activate s transcription in the presence of CREB. The C/EBP-alpha-mediated acti vation is antagonized by COUP-TF. The positive action of the cAMP resp onse element-binding protein called CRI-BP is revealed by mutations of the central region I site which repress transcription. Moreover addit ion 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.