Negative cyclic AMP response elements in the promoter of the L-type pyruvate kinase gene.
L-type pyruvate kinase gene expression is modulated by hormonal and nutritional conditions. Here, we show by transient transfections in hepatocytes in primary culture that both the glucose response element and the contiguous hepatocyte nuclear factor 4 (HNF4) binding site (L3) of the promoter were negative cyclic AMP (cAMP) response elements and that cAMP-dependent inhibition through L3 requires HNF4 binding. Another HNF4 binding site-dependent construct was also inhibited by cAMP. However, HNF4 mutants whose putative PKA-dependent phosphorylation sites have been mutated still conferred cAMP-sensitive transactivation of a L3-dependent reporter gene. Overexpression of the CREB binding protein (CBP) increased the HNF4-dependent transactivation but this effect remained sensitive to cAMP inhibition.
Gourdon
L
L
Unité de Recherches en Physiologie et Pathologie Génétiques et Moléculaires, Institut Cochin de Génétique Moléculaire, INSERM Unité 129, 24 rue du Faubourg Saint Jacques, 75014, Paris, France.
Lou
D Q
DQ
Raymondjean
M
M
Vasseur-Cognet
M
M
Kahn
A
A
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic; D051557:Hepatocyte Nuclear Factor 4; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D014157:Transcription Factors; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D017868:Cyclic AMP-Dependent Protein Kinases