Mechanism of specific expression of glutathione transferase P gene during hepatocarcinogenesis.
The mechanism of specific expression of glutathione transferase P gene during hepatocarcinogenesis of the rat has been investigated by cloning the gene and determining the upstream regulatory sequences. Two enhancers and a silencer are located within 3 kb upstream of the promoter. The stronger enhancer designated GPEI has two TPA (12-O-tetradecanoyl phorbol 13-acetate)-response element (TRE)-like sequences arranged in a palindrome at a 3 base pairs spacing. This special combination was found to form a very strong enhancer which could act efficiently even in F9 cells where the collagenase enhancer with a singlet TRE cannot work due to the low c-jun content. Whether this structure is operating with a very low concentration of c-jun/c-fos heterodimer or with any other proteins remains to be determined. These findings suggest that new and more efficient enhancers evolve by a combination of basic enhancer elements. The silencer region consists of several sequences that can bind specific protein(s) and works cooperatively.
Muramatsu
M
M
Department of Biochemistry, University of Tokyo Faculty of Medicine, Japan.
Okuda
A
A
Morimura
S
S
Osada
S
S
Diccianni
M B
MB
Imagawa
M
M
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003851:Deoxyribonucleases / Q000032:analysis; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics*; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D005982:Glutathione Transferase; D003851:Deoxyribonucleases