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 glycoprotein which controls the activation of the complement cascade through the classical pathway. In humans, the majority form of C4BP is composed of seven alpha-chains and one beta-chain, covalently linked by their C-termini. C4BP is mainly expressed in the liver. We have previously cloned and characterized the structure of the genes encoding the alpha and beta chains, C4BPA and C4BPB, respectively. Here we addressed the characterization of the mechanisms controlling the hepatic restricted expression of the C4BPA gene. We found that the C4BPA promoter is contained within the first 369 bp upstream of the transcription start site. The activity of this promoter is restricted to hepatic cells in transfection experiments. The hepatic transcription factor HNF1 interacts with a region of this promoter at -38 bp. This region is absolutely required for the activity of this promoter, suggesting that HNF1 is essential for the hepatic activity of the C4BPA promoter. We speculate that this extreme requirement of HNF1 for the activity of the human C4BPA promoter is related to the fact that this promoter lacks a TATA box.
Arenzana
N
N
Departamento de Inmunología, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Rodríguez de Córdoba
S
S
Rey-Campos
J
J
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D003169:Complement Inactivator Proteins; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006023:Glycoproteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C496489:Hnf1a protein, rat; C496496:Hnf1b protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta