Operon Model: Regulation of Gene Expression in E. coli
Operon Model: Regulation of Gene Expression
Operon Model: Studies on the control of mRNA synthesis from initiation and the glucose effect observed in Monod’s work (1947) revealed that when glucose was added to a bacterial culture of E. coli containing lactose, the level of galactosidase significantly decreased.
This enzyme, galactosidase, separates lactose into its components: galactose and glucose. If bacteria are growing and glucose is added to the medium, the need to break down lactose decreases, and the enzyme level decreases. Later, in the 1950s, Jacob and Monod, working with E. coli, discovered that the enzymes suppressed in the experiment were β-galactosidase, permease, and β-galactosidase transacetylase. These three enzymes are involved in lactose metabolism. The presence of the substrate (lactose) represses all enzymes of a metabolic pathway. In 1961, Jacob and Monod proposed the operon model to explain the control of protein synthesis.
According to this model, there are two types of genes:
- Structural genes: Encode structural and enzymatic proteins.
- Regulatory genes: Encode proteins whose activity controls the structural genes. These proteins are called repressors.
Example: The lactose operon of E. coli consists of a regulatory gene and three structural genes. Before these genes is the promoter region, which is the junction between RNA polymerase and the genes. Adjacent to this region is the operator, where the repressor binds. In this case, the repressor protein binds to the operator, preventing RNA polymerase from proceeding. Transcription is prevented, and thus, protein synthesis is inhibited.
If lactose is present, it acts as an inducer. It binds to the repressor protein, allowing RNA polymerase to proceed freely. Therefore, transcription and protein synthesis occur.
Control of cAMP
cAMP is formed from ATP by the enzyme adenylate cyclase, located on the inside of the cell membrane. For cAMP to act, it needs CAP (catabolite activator protein). The CAP + cAMP complex has an affinity for a promoter region where RNA polymerase binds. Without this complex, RNA polymerase has difficulty binding to the promoter.
It has been observed that when glucose levels increase in the cell, the level of cAMP decreases. Hence, without CAP-cAMP, there is no transcription, and the enzymes for lactose metabolism are not synthesized. Therefore, if there is no glucose present and lactose is available, the enzymes for lactose metabolism can be synthesized.
In eukaryotic cells, gene expression responds to hormonal changes in the internal environment. Depending on the cell type, there will be different membrane receptors, targeting specific cells to certain hormones. The control of gene expression differs depending on whether the hormones are lipid or protein hormones.
Lipid Hormones
Lipid hormones, such as steroid hormones, can easily cross the cell membrane and bind to receptor proteins in the cytoplasm. They form a hormone-receptor complex that goes to the nucleus and binds to a specific sequence of DNA, initiating transcription in that region.
Protein Hormones
Protein hormones are larger and cannot cross the membrane. They bind to receptor proteins on the membrane, forming a hormone-receptor complex. This activates adenylate cyclase, which is on the inside of the membrane and converts ATP into cAMP. cAMP then goes to the nucleus and regulates transcription.