Nucleic Acids Research, 1992, Vol. 20, No. 8 1871-1878
© 1992
MOLECULAR BIOLOGY |
Cis-regulation of the L-type pyruvate kinase gene promoter by glucose, insulin and cyclic AMP
ICGM, Laboratoire de recherches en Génétique et pathologie Moléculaire INSERM U.129, CHU Cochin, 24 rue du faubourg Saint Jacques, 75014 Paris, France
To whom correspondence should be addressed
Received February 7, 1992. Revised March 26, 1992. Accepted March 26, 1992.
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.
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