Isolation oftwocDNAsencoding zincfinger proteins which bindtothea1-antitrypsin promoter andtothemajor histocompatibili ty complex class Ienhancer

ABSTRACTTwo partial cDNAs coding for DNA-binding proteins (AT-BP1 and AT-BP2) have been isolated. Bothproteins, when preparedfrom Xgtl 1 lysogens, bindto the B-domain of the a1-antitrypsin promoter, an element which is important for the liver-specific expression of a1-antitrypsin. Analysis of the cDNAsequences encodingthese proteins revealsthat both contain two zincfingers of theCys2-His2 typefollowed by a highly acidic stretch of 20aminoacids. AT-BP1 contains a second putative DNA-binding domainconsisting of an 8-fold repeat of a SPKK (Ser-Pro-Lys/Arg-Lys/Arg) motif. Bothproteins bind to the NF- xB recognition site in the MHC gene enhancer with significantly higher affinity than to the x immunoglobulin geneenhancer,ortothe B-domain of the a,-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 beelucidated, theirpredictedamino acid sequence and their DNA-binding characteristics