The rat mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal regulation and tissue specificity

Eur J Biochem. 1993 Apr 15;213(2):773-9. doi: 10.1111/j.1432-1033.1993.tb17819.x.


Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) synthase, a liver-specific enzyme, is a constituent of the HMG-CoA cycle responsible for ketone-body synthesis. We report the isolation and characterization of genomic clones that encompass the gene for rat mitochondrial HMG-CoA synthase. The gene spans at least 24 kbp and contains ten exons and nine introns. The 5' flanking region of the gene has also been cloned and characterized. Exon 1 contains the untranslated sequence of the transcript, extending downstream to enclose the coding region for the putative mitochondrial-targeting signal (35 amino acids). The 1149-bp proximal region of the transcription start point permits transcription of a reporter gene in transfected hepatoma cells but not in an extrahepatic cell line, confirming the function of the promoter. A truncated construct of 142 bp is still able to promote transcription in hepatoma cells, suggesting the presence of liver-specific enhancer elements in the proximal promoter region. The 5' flanking region contains typical promoter elements, including a TATA box and several putative recognition sequences for transcription factors involved in controlling both basal-level and hormone-modulated transcription rates. Furthermore, the presence in the mitochondrial HMG-CoA-synthase promoter of cis-elements, responsible for the multihormonal regulation of transcription, is supported by transient transfection experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Cyclic AMP / pharmacology
  • Dexamethasone / pharmacology*
  • Exons
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Genomic Library
  • Humans
  • Hydroxymethylglutaryl-CoA Synthase / genetics*
  • Hydroxymethylglutaryl-CoA Synthase / metabolism
  • Insulin / pharmacology*
  • Introns
  • Mitochondria, Liver / enzymology*
  • Molecular Sequence Data
  • Oleic Acid
  • Oleic Acids / pharmacology
  • Oligodeoxyribonucleotides
  • Organ Specificity
  • Plasmids
  • Promoter Regions, Genetic
  • RNA Splicing
  • Rats
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured


  • Insulin
  • Oleic Acids
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Oleic Acid
  • Dexamethasone
  • Cyclic AMP
  • Hydroxymethylglutaryl-CoA Synthase

Associated data

  • GENBANK/D14867
  • GENBANK/D14868
  • GENBANK/L09679
  • GENBANK/L09680
  • GENBANK/L09681
  • GENBANK/L09682
  • GENBANK/L09683
  • GENBANK/M63800
  • GENBANK/X57950
  • GENBANK/X71000