Expression of the L-type pyruvate kinase gene and the hepatocyte nuclear factor 4 transcription factor in exocrine and endocrine pancreas.
The L-pyruvate kinase (L-PK) gene is slightly active in normal and tumoral endocrine pancreatic tissues while, in vivo, this gene is not transcribed in the exocrine pancreas. Nevertheless, the L-PK gene is re-expressed at a very low level in cultured 266.6 cells derived from an exocrine pancreas carcinoma. The L-PK gene is early activated in endodermal tissues, e.g. yolk sac and primitive intestine; it remains transcribed in fetal pancreas. In adult, L-PK gene expression is restricted to some endocrine cells. Hepatocyte nuclear factor (HNF) 1 and HNF4 are the main tissue-restricted transcription factors involved in tissue-specific expression of the L-PK gene. HNF1 concentration is similar in liver and all pancreatic cells. HNF4 concentration is high in liver, much lower in islets of Langerhans, endocrine pancreatic tumors, and cultured insulinoma cells, and is scarcely detectable in adult exocrine pancreas. This distribution of HNF4 parallels the expression of the L-PK gene. In vivo footprinting experiments show that the HNF1 binding site is similarly occupied in both adult liver and adult pancreas, in which this gene is practically inactive. In this latter tissue, however, the HNF4 binding site is differently occupied with respect to the liver. Since the chromatin structure remains open around the L-PK promoter in pancreas, the L-PK gene can probably be re-expressed under certain circumstances, for instance in cancerous pancreatic cells.
Miquerol
L
L
Institut Cochin de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 129, Paris, France.
Lopez
S
S
Cartier
N
N
Tulliez
M
M
Raymondjean
M
M
Kahn
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D007515:Islets of Langerhans / Q000166:cytology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010179:Pancreas / Q000166:cytology*; D010750:Phosphoproteins; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D011770:Pyruvate Kinase