title: Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene.
abstract: We report the characterization of lambda and P1 phage clones containing the entire human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase (mHS) gene. The human mHS locus (HMGCS2) on chromosome 1p12-13 spans 25 kb and contains 10 exons. Exon 1 contains most of the mitochondrial leader, consistent with a recent hypothesis of the evolution of the ketogenic pathway. By primer extension and cDNA amplification (RACE-PCR) we localized the transcription start point (tsp) to 60 bp upstream of the initiation codon. Nine blocks of conserved sequence were identified by comparing the 5' flanking regions of the mHS genes of human and rat. The 5' flanking region contains potential binding sites for TATA-binding protein, Sp1, nuclear factor 1 (NF1), CAAT-box binding protein (C/EBP), hepatocyte nuclear factors 1 and 5 (HNF1, HNF5) and activator proteins 1 and 2 (AP1, AP2).
authors.affiliation: Service de génétique médicale, Hôpital Ste-Justine, Université de Montréal, Québec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Boukaftane
authors.forename: G A
authors.initials: GA
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D017101:Bacteriophage P1 / Q000235:genetics; D010582:Bacteriophage lambda / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D018387:Codon, Initiator; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D007652:Oxo-Acid-Lyases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D021382:Protein Sorting Signals / Q000235:genetics; D051381:Rats; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000235:genetics; D016385:TATA Box; D018808:Transcription Factor AP-1 / Q000235:genetics; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D018387:Codon, Initiator; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C000599408:HMGCS2 protein, human; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D006904:Hydroxymethylglutaryl-CoA Synthase; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase