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Nucleic Acids Research, 1991, Vol. 19, No. 1 141-147
© 1991


MOLECULAR BIOLOGY

Isolation of two cDNAs encoding zinc finger proteins which bind to the {alpha}1antitrypsin promoter and to the major histocompatibility complex class I enhancer

Catherine Mitchelmore*, Cinzia Traboni1 and Riccardo Cortese+

1Dipartmento Biopatologia Policlinico Umberto I, Rome, Italy European Molecular Biology Laboratory Meyerhofstraße 1, 6900-Heiddberg, FRG

*To whom correspondence should be addressed

Received August 15, 1990. Revised September 27, 1990. Accepted September 27, 1990.

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-xB recognition site in the MHC gene enhancer with significantly higher affinity than to the x 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.


+Present address: Institute Ricerche di Biologia Molecolare, Via Pontina Km 30.6, Pomezia, Italy


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