LIVER-ENRICHED HNF-3-ALPHA AND UBIQUITOUS FACTORS INTERACT WITH THE HUMAN TRANSFERRIN GENE ENHANCER

The human transferrin gene enhancer is organized in two domains. Domai n A contains a single enhanson designated Ia. Domain B contains four e nhansons named Ib, II, III and IV. We demonstrate here that the liver- enriched transcription factor HNF-3alpha interacts with enhanson Ia an d that enhansons Ib and IV are binding sites for members of the NF1 fa mily. In addition, enhansons II and III seem to be respectively the ta rgets for the AP4 protein and for EIII, a factor not yet completely id entified. Analysis of mutated enhancer regions establishes that each e nhanson is required for full enhancer activity and that the proteins b inding to enhansons II, III and IV may interact within a multiprotein complex. This enhancer region presents no activity in the Sertoli cell s of testis, where transferrin is also synthesized. We demonstrate tha t in Sertoli cells, the members of the HNF-3 family are not expressed; this fact may account for the inactivity of the enhancer in these cel ls.