THE RAT MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A-SYNTHASE GENE CONTAINS ELEMENTS THAT MEDIATE ITS MULTIHORMONAL REGULATION AND TISSUE-SPECIFICITY
G. Gilgomez et al., THE RAT MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A-SYNTHASE GENE CONTAINS ELEMENTS THAT MEDIATE ITS MULTIHORMONAL REGULATION AND TISSUE-SPECIFICITY, European journal of biochemistry, 213(2), 1993, pp. 773-779
Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A HMG-CoA) synthase,
a liver-specific enzyme, is a constituent of the HMG-CoA cycle respon
sible for ketone-body synthesis. We report the isolation and character
ization of genomic clones that encompass the gene for rat mitochondria
l HMG-CoA synthase. The gene spans at least 24 kbp and contains ten ex
ons and nine introns. The 5' flanking region of the gene has also been
cloned and characterized. Exon 1 contains the untranslated sequence o
f the transcript, extending downstream to enclose the coding region fo
r the putative mitochondrial-targeting signal (35 amino acids). The 11
49-bp proximal region of the transcription start point permits transcr
iption of a reporter gene in transfected hepatoma cells but not in an
extrahepatic cell line, confirming the function of the promoter. A tru
ncated construct of 142bp is still able to promote transcription in he
patoma cells, suggesting the presence of liver-specific enhancer eleme
nts in the proximal promoter region. The 5' flanking region contains t
ypical promoter elements, including a TATA box and several putative re
cognition sequences for transcription factors involved in controlling
both basal-level and hormone-modulated transcription rates. Furthermor
e, the presence in the mitochondrial HMG-CoA-synthase promoter of cis-
elements, responsible for the multihormonal regulation of transcriptio
n, is supported by transient transfection experiments.