Jacob-Monod hypothesisa concept of gene regulation proposed by the French biochemists François Jacob and Jacques Monod in the late 1950s. Using strains of E. coli mutant at the lac locus, they demonstrated that production of (β-galactosidase occurs only in the presence of lactose, an example of ENZYME INDUCTION, and proposed a new organization of related genes. The model has the following components: an operon consisting of at least one structural gene coding for primary enzyme structure, and two regulatory elements, one called the operator and the other called the PROMOTER that binds with RNA POLYMERASE so that TRANSCRIPTION can be initiated. The model proposes the presence of a regulator gene producing a repressor protein that binds with the operator, so inhibiting (repressing) transcription of the structural genes.
When a state of enzyme repression is in operation, the repressor is bound to the operator and blocks RNA polymerase, so preventing the formation of MESSENGER RNA from the structural genes. It should be noted that transcription is rarely turned off completely: a basal level of transcription occurs with minimal synthesis of the structural gene products (see Fig. 235 ). However, the introduction of a suitable inducer substance (e.g. the substrate of the enzyme coded by the structural gene) causes an inducer-repressor complex to be formed. Binding of the inducer to the repressor causes a change in conformation of the repressor and it is released from the operator. Thus the operator site is no longer blocked and RNA polymerase can bind to the promoter and move along the operon, transcribing the structural gene(s) and producing POLYCISTRONIC mRNA, a process called enzyme induction (see Fig. 236 ).
When the inducer level falls (having been metabolized by the enzyme) the operator becomes blocked again by the repressor so that the structural genes are now repressed, an example of a negative control mechanism. The operon model has been extended to encompass a system of enzyme repression where structural genes are active normally only becoming repressed when too much product is present. Furthermore, although the operon model was developed from bacterial studies, the system has been incorporated into general ideas about CELL DIFFERENTIATION in eukaryotes, in which GENE SWITCHING occurs in an orderly manner throughout development, as may be seen in the sequences of CHROMOSOME PUFFS that occur in some insects.