A cis-active regulatory gene in the mouse: direct demonstration of cis-active control of the rate of enzyme subunit synthesis
Mouse mitochondrial malic enzyme (L-malate:NADP/sup +/ oxidoreductase (oxaloacetate-decarboxylating), EC1.1.1.40) is a tetrameric protein. Two alleles of the structural gene (Mod-2) are known which code for electrophoretically distinct enzyme subunits: Mod-2/sup a/ and Mod-2/sup b/. A regulatory gene (Mdr-1), closely linked to Mod-2 on chromosome 7, determines the rate of mitochondrial malic enzyme synthesis in brain. Two alleles of Mdr-1 are known: Mdr-1/sup a/ (high activity) and Mdr-1/sup b/ (low activity). By pulse-labeling with (/sup 35/S)methionine, immune precipitation, and isoelectric focusing under dissociating conditions, we have measured the relative rates of synthesis of the two types of enzyme subunit in animals of genotypes Mdr-1/sup a/ Mod-2/sup a//Mdr-1/sup a/ Mod-2/sup b/ and Mdr-1/sup a/ Mod-2/sup a//Mdr-1/sup b/ Mod-2/sup b/. The results show that in the former animals both types of subunit are made at an identical rate, whereas in the latter animals the Mod-2/sup a/ gene product is synthesized at a rate 2.2 times that of the Mod-2/sup b/-coded subunit. Thus we have unambiguously demonstrated that Mdr-1 is cis-active in its control of the expression of the Mod-2 structural gene.
- Research Organization:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 5127375
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 77:7
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ENZYME ACTIVITY
GENETIC VARIABILITY
OXIDOREDUCTASES
BIOSYNTHESIS
BRAIN
GENES
GENETICS
GENOTYPE
IMMUNE REACTIONS
LABELLED COMPOUNDS
METHIONINE
MICE
MITOCHONDRIA
SULFUR 35
TRACER TECHNIQUES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL VARIABILITY
BIOLOGY
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
ENZYMES
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
NERVOUS SYSTEM
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANOIDS
ORGANS
RADIOISOTOPES
RODENTS
SULFUR ISOTOPES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
551001 - Physiological Systems- Tracer Techniques
550401 - Genetics- Tracer Techniques