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 H MG-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-acti vated by the peroxisomal proliferator-activated receptor (PPAR), and a func tional response element for PPAR (PPRE) has been localized in the promoter region. Pig PPRE is constituted by an imperfect direct repeat (DR-I) 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 rec eptor heterodimers. A role of PPAR trans-activation in starvation associate d induction of gene expression is suggested.