A cis-active regulatory gene in the mouse: direct demonstration of cis-active control of the rate of enzyme subunit synthesis.

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Abstract
Mouse mitochondrial malic enzyme [L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 1.1.1.40] is a tetrameric protein. Two alleles of the structural gene (Mod-2) code for electrophoretically distinct enzyme subunits: Mod-2a and Mod-2b. 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-1a (high activity) and Mdr-1b (low activity). By pulse-labeling with [35S]methionine, immune precipitation and isoelectric focusing under dissociating conditions, the relative rates of synthesis of the 2 types of enzyme subunit in animals of genotypes Mdr-1a Mod-2a/Mdr-1a Mod-2b and Mdr-1a Mod-2a/Mdr-1b Mod-2b were measured. In the former animals, both types of subunit are made at an identical rate, whereas in the latter animals the Mod-2a gene product is synthesized at a rate 2.2 .times. that of the Mod-2b-coded subunit. Mdr-1 is cis-active in its control of the expression of the Mod-2 structural gene.