Different liver nuclear proteins bind to similar DNA sequences in the 5' flanking regions of three hepatic genes

Abstract The proximal promoter region of the human transferrin gene contains an hepatocyte-specific cis-element (PRI, nucleotides -76 to -51) whose DNA sequence is homologous to a sequence (nucleotides -89 to -68) present in the transcriptionally essential 5' region of the human antithrombin III gene and to another hepatocyte-specific sequence (A domain) of the human alpha 1-antitrypsin gene promoter. The results reported here lead to the conclusion that the liver trans-acting factor Tf-LF1, binding to the transferrin PRI cis-element interacts with the homologous antithrombin III region, but is different from the transcription factor LF-A1 interacting with the A domain of the alpha 1-antitrypsin promoter. The distal region DRI (nucleotides -480 to -454) of the human transferrin gene promoter presents in its core the same 10 nucleotide-long sequence as the PRI cis-element. We have previously shown that the liver protein Tf-LF2, binding to the DRI element is different from the Tf-LF1 trans-acting factor. In this paper we also show that Tf-LF2 is different from the transcription factor LF-A1 interacting with the alpha 1-antitrypsin promoter. The results allow us to conclude that at least three distinct liver nuclear proteins bind to different subsets of 5' DNA regions containing similar sequences. These sequences are present in genes expressed essentially in liver.