EXPRESSION OF THE HUMAN GENE CODING FOR THE ALPHA-CHAIN OF C4B-BINDING PROTEIN, C4BPA, IS CONTROLLED BY AN HNF1-DEPENDENT HEPATIC-SPECIFIC PROMOTER

C4b-binding protein (C4BP) is an abundant oligomeric plasma glycoprote in which controls the activation of the complement cascade through the classical pathway. In humans, the majority form of C4BP is composed o f seven alpha-chains and one beta-chain, covalently linked by their C- termini. C4BP is mainly expressed in the liver. We have previously clo ned and characterized the structure of the genes encoding the alpha an d beta chains, C4BPA and C4BPB, respectively. Here we addressed the ch aracterization of the mechanisms controlling the hepatic restricted ex pression of the C4BPA gene. We found that the C4BPA promoter is contai ned within the first 369 bp upstream of the transcription start site. The activity of this promoter is restricted to hepatic cells in transf ection experiments. The hepatic transcription factor HNF1 interacts wi th a region of this promoter at -38 bp. This region is absolutely requ ired for the activity of this promoter, suggesting that HNF1 is essent ial for the hepatic activity of the C4BPA promoter. We speculate that this extreme requirement of HNF1 for the activity of the human C4BPA p romoter is related to the fact that this promoter lacks a TATA box.