Functional analysis of zinc finger proteins that bind to the silencer element in the glutathione transferase P gene.
Glutathione transferase P (GST-P) gene expression is repressed in normal rats but markedly promoted during the early stage of chemical hepatocarcinogenesis. We have previously identified a silencer region in this gene promoter. The silencer is composed of several cis-elements to which at least three proteins (Silencer factor-A, -B, and -C: SF-A, SF-B, and SF-C) are known to bind. We cloned and characterized the nuclear factor 1 family and the CCAAT/enhancer-binding protein family as SF-A and SF-B, respectively. Recently, zinc finger proteins as candidates for SF-C, which binds to GST-P silencer 2 (GPS2), were isolated. These proteins include four Krüppel-like proteins (BTEB2, EZF, LKLF, and TIEG1) and other factors containing multiple zinc finger motifs (TFIIIA and MZFP). In the present study, we found that the zinc finger proteins showed the same DNA-binding affinities to GPS2. Moreover, transfection analyses revealed that BTEB2, EZF, and TIEGI repressed the GST-P promoter activity. Therefore, these three factors might contribute to the repression of the GST-P gene expression in normal rat liver.
Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka, Suita, Japan.
Atsuhiro
A
Tanabe
Mitsumasa
M
Kurita
Kazumi
K
Oshima
Shigehiro
S
Osada
Tsutomu
T
Nishihara
Masayoshi
M
Imagawa
D000595:Amino Acid Sequence; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000090062:Kruppel-Like Factor 4; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D037941:Silencer Elements, Transcriptional / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
C103316:GPS2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C000715467:KLF4 protein, human; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D012097:Repressor Proteins; D005982:Glutathione Transferase