Identification of zinc finger proteins bound to a silencer region in the rat glutathione transferase P gene

The rat glutathione transferase P (GST-P) gene is strongly induced during c hemical hepatocarcinogenesis, whereas mRNA of this gene is rarely expressed in normal rat liver. We previously identified a silencer region in the pro moter of this gene. This silencer has several DNA binding sites and at leas t three proteins (Silencer factor-A, -B, and -C (SF-A, SF-B, and SF-C)) bin d to these sites. We previously cloned and characterized the Nuclear Factor 1 (NF1) family and the CCAAT/enhancer-binding protein (C/EBP) family as SF -A and SF-B, respectively. However, SF-C which binds to GST-P silencer 2 (G PS2) remains to be cloned, By screening using yeast one-hybrid system, seve ral zinc finger proteins were identified as a candidate of SF-C, The gel-mo bility shift analyses showed that BTEB2, EZF, LKLF, TFIIIA, TIEG1, and nove l zinc finger protein MZFP bound to GPS2 with different affinities. Several proteins of these are known to be transcriptional activators or repressors , suggesting that zinc finger proteins bind to GPS2 and regulate GST-P expr ession in the rat liver.