Isolation of two 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 alpha 1-antitrypsin promoter, an element which is important for the liver-specific expression of alpha 1-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 alpha 1-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.
Mitchelmore
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C
European Molecular Biology Laboratory, Heidelberg, FRG.
Traboni
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Cortese
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R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005805:Genes, MHC Class I; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000515:alpha 1-Antitrypsin; C068169:alpha 1-antitrypsin binding protein 1; C068168:alpha 1-antitrypsin binding protein 2; D004247:DNA; D001616:beta-Galactosidase