The peroxisome proliferator activated receptor regulates malic enzyme gene expression.
A new regulatory element for peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR) heterodimers was found in the promoter of the malic enzyme gene. Similar to previously characterized peroxisome proliferator response elements (PPREs), it consists of a direct repeat of sequences related to the half-site consensus AGGTCA with an interspacing of 1 base pair. Specific binding of PPAR/RXR heterodimers to this element was demonstrated. Furthermore, this sequence conferred ciprofibrate responsiveness of a reporter through the homologous malic enzyme or heterologous thymidine kinase promoters. This PPRE presumably mediates the transcriptional effects of peroxisome proliferators on malic enzyme expression. The presence of a PPRE in the promoter of this lipogenic enzyme suggests a broader function for the PPAR in the regulation of lipid metabolism.
Castelein
H
H
Laboratory of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Catholic University of Leuven, Belgium.
Gulick
T
T
Declercq
P E
PE
Mannaerts
G P
GP
Moore
D D
DD
Baes
M I
MI
D000818:Animals; D001483:Base Sequence; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004252:DNA Mutational Analysis; D058607:Fibric Acids; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008291:Malate Dehydrogenase / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D002995:Clofibric Acid; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating); C019304:ciprofibrate