BRAIN-SPECIFIC EXPRESSION OF THE HUMAN TRANSFERRIN GENE - SIMILAR ELEMENTS GOVERN TRANSCRIPTION IN OLIGODENDROCYTES AND IN A NEURONAL CELL-LINE

We have identified the regulatory sequences that govern the expression of the human transferrin gene in cultured brain cells and compared th em with the data obtained with the neuronal cell line B103. Oligodendr ocytes and epithelial choroid plexus cells from rat brain were culture d and used for transient expression experiments. Deletion analysis of 1.8 kilobase pairs of the 5' regulatory sequences revealed a -1530/-11 40 positive-acting region in oligodendrocytes. The -164/+1 promoter re gion was sufficient to confer cell type-specific transcription in olig odendrocytes, epithelial choroid plexus cells, and B103 cells. DNase I footprinting experiments revealed three protected sequences, the prox imal regions I and II, and the central region I. Gel retardation and a ntibody reactivity data allowed us to identify most of the nuclear fac tors present in oligodendrocytes interacting with the promoter sequenc es. Chicken ovalbumin upstream promoter transcription factor, a CAAT/e nhancer-binding protein, and a cAMP response element-binding protein c alled CRI-BP interact with the proximal regions I and II and central r egion I sites, respectively. These data confirm the results obtained w ith the neuronal cell line and emphasize the importance of the three p romoter elements for the transferrin gene-specific expression in the c entral nervous system compared with only two elements required for liv er- and testis-specific expression.