Isolation of pig mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene promoter: characterization of a peroxisome proliferator-responsive element.
Low expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene during development correlates with an unusually low hepatic ketogenic capacity and lack of hyperketonaemia in piglets. Here we report the isolation and characterization of the 5' end of the pig mitochondrial HMG-CoA synthase gene. The 581 bp region proximal to the transcription start site permits transcription of a reporter gene, confirming the function of the promoter. The pig mitochondrial HMG-CoA synthase promoter is trans-activated by the peroxisomal proliferator-activated receptor (PPAR), and a functional response element for PPAR (PPRE) has been localized in the promoter region. Pig PPRE is constituted by an imperfect direct repeat (DR-1) and a downstream sequence, both of which are needed to confer PPAR-sensitivity to a thymidine kinase promoter and to form complexes with PPAR.retinoid X receptor heterodimers. A role of PPAR trans-activation in starvation-associated induction of gene expression is suggested.
Ortiz
J A
JA
Departamento de Bioqu approximately ímica y Biolog approximately ía Molecular, Facultad de Farmacia, Universidad de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain.
Mallolas
J
J
Nicot
C
C
Bofarull
J
J
Rodríguez
J C
JC
Hegardt
F G
FG
Haro
D
D
Marrero
P F
PF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics*; D050356:Lipid Metabolism; D008928:Mitochondria / Q000201:enzymology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020025:Peroxisome Proliferators / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020218:Response Elements; D047488:Retinoid X Receptors; D013045:Species Specificity; D013552:Swine / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D020025:Peroxisome Proliferators; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D006904:Hydroxymethylglutaryl-CoA Synthase