CLONING AND CHARACTERIZATION OF THE HUMAN MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL COA SYNTHASE GENE

We report the characterization of lambda and P1 phage clones containin g the entire human mitochondrial 3-hydroxy-3-methylglutaryl CoA syntha se (mHS) gene. The human mHS locus (HMGCS2) on chromosome 1p12-13 span s 25 kb and contains 10 exons. Exon 1 contains most of the mitochondri al leader, consistent with a recent hypothesis of the evolution of the ketogenic pathway. By primer extension and cDNA amplification (RACE-P CR) we localized the transcription start point (tsp) to 60 bp upstream of the initiation codon. Nine blocks of conserved sequence were ident ified by comparing the 5' flanking regions of the mHS genes of human a nd rat. The 5' flanking region contains potential binding sites for TA TA-binding protein, Spl, nuclear factor 1 (NF1), CAAT-box binding prot ein (C/EBP), hepatocyte nuclear factors 1 and 5 (HNF1, HNF5) and activ ator proteins 1 and 2 (AP1, AP2). (C) 1997 Elsevier Science B.V.