A specific distal promoter controls gamma-glutamyl transpeptidase gene expression in undifferentiated rat transformed liver cells.
In rat undifferentiated hepatoma cells, the gamma-glutamyl transpeptidase (GGT) gene is transcribed into a 2.3 and a 2.6 kb mRNA which, in contrast with other rat GGT transcripts, are not detected in more differentiated liver cells or adult tissues. Analysis of the cDNA sequences obtained from H5 hepatoma cells reveals that these two transcripts differ from other GGT mRNAs by a 312-nt unique untranslated leader sequence; this sequence maps on the gene in a single exon 10 kb upstream from the GGT promoter IV transcription start site. We established that the 2.6 kb mRNA V-1 and the 2.3 kb GGT mRNA V-2 derive, by alternate splicing, from a primary transcript initiated on a distal promoter on the rat GGT gene. This gene appears to be transcribed from five promoters, and the specific expression of this new distal promoter in undifferentiated hepatoma cells requires binding of activator protein-1 and hepatic nuclear factor 3 specific transcription factors to a composite cis-element in the proximal region of the promoter. The distal GGT promoter, specifically expressed in undifferentiated liver cells, might reflect the expression of that gene in liver precursor cells before they differentiate in the hepatocytic or biliary lineage.
Nomura
S
S
Institut National de la Santé et de la Recherche Médicale, Unité 99, Hôpital Henri Mondor, Créteil, France.
Lahuna
O
O
Suzuki
T
T
Brouillet
A
A
Chobert
M N
MN
Laperche
Y
Y
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D051543:Hepatocyte Nuclear Factor 3-gamma; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D005723:gamma-Glutamyltransferase / Q000737:chemistry / Q000235:genetics*
D004268:DNA-Binding Proteins; C496507:Foxa3 protein, rat; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051543:Hepatocyte Nuclear Factor 3-gamma; D005723:gamma-Glutamyltransferase