ISOLATION OF 2 CDNAS ENCODING ZINC FINGER PROTEINS WHICH BIND TO THE ALPHA-1-ANTITRYPSIN PROMOTER AND TO THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ENHANCER

Two partial cDNAs coding for DNA-binding proteins (AT-BP1 and AT-BP2) have been isolated. Both proteins, when prepared from lambda-gt11 lysogens, bind to the B-domain of the alpha1-antitrypsin promoter, an element which is important for the liver-specific expression of alpha1-antitrypsin. Analysis of the cDNA sequences encoding these proteins reveals that both contain two zinc fingers of the Cys2-His2 type followed by a highly acidic stretch of 20 amino acids. At-BP1 contains a second putative DNA-binding domain consisting of an 8-fold repeat of a SPKK (Ser-Pro-Lys/Arg-Lys/Arg) motif. Both proteins bind to the NF-kappa-B recognition site in the MHC gene enhancer with significantly higher affinity than to the kappa immunoglobulin gene enhancer, or to the B-domain of the alpha1-antitrypsin gene promoter. Analysis of mRNA expression shows that AT-BP1 and AT-BP2 are expressed in all the tissues examined. While the physiological roles of AT-BP1 and AT-BP2 remain to be elucidated, their predicted amino acid sequence and their DNA-binding characteristics suggest a role as transcriptional regulators.