Cis-regulation of the L-type pyruvate kinase gene promoter by glucose, insulin and cyclic AMP.
The glucose/insulin response element of the L-pyruvate kinase gene is a perfect palindrome located from nt -168 to -144 with respect to the cap site. This element (L4) is partially homologous to MLTF binding sites. Its full efficiency requires cooperation with a contiguous binding site for HNF4, termed L3 and located from nt -145 to -125. In the presence of the L4 element contiguous to L3, cyclic AMP inhibits activity of the L-PK promoter while in its absence, or when the normal L4-L3 contiguity is modified, cyclic AMP behaves as a transcriptional activator that does not seem to be sequence-specific. Therefore, we propose that the mechanism of inhibition of the L-PK gene by cyclic AMP requires precise interactions between the nucleoprotein complex built up at sites L4 and L3 and other components of the L-PK transcription initiation complex.
Bergot
M O
MO
ICGM, Laboratoire de recherches en Génétique et pathologie Moléculaire, INSERM U.129, CHU Cochin, Paris, France.
Diaz-Guerra
M J
MJ
Puzenat
N
N
Raymondjean
M
M
Kahn
A
A
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011770:Pyruvate Kinase / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
D007328:Insulin; D011993:Recombinant Fusion Proteins; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D005947:Glucose