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

Authors: Gil-Gomez, G  Ayte, J  Hegardt, FG 
Citation: Gil-Gomez G, etal., Eur J Biochem 1993 Apr 15;213(2):773-9.
Pubmed: (View Article at PubMed) PMID:8097464

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.

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CRRD Object Information
CRRD ID: 728598
Created: 2003-11-19
Species: All species
Last Modified: 2003-11-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.