Gene Regulation Overview

Gene Regulation Overview

• Bacterial genomes encode thousands of proteins, but cells don't express all at maximum levels. This is due to physical limitations, energy/resource conservation, and contradictory functions.
• Gene regulation occurs at multiple levels: altering DNA sequence, controlling transcription, mRNA stability, translational control, and post-translational control.

Transcriptional Regulation

• Transcription initiation is a major regulatory point in bacteria.
• Regulatory proteins bind DNA near gene promoters, influencing RNA polymerase binding.
• These proteins often interact with the DNA major groove as dimers, binding to symmetrical DNA sequences (inverted repeats).
• Changes in the intracellular environment are detected by regulatory proteins binding to low-molecular-weight molecules (ligands).
• Regulatory protein genes are transcribed separately from target genes.

Repressors and Activators

• Repressors prevent gene expression by binding to operators (DNA sequences). Some repressors bind without a ligand, while others require ligand binding (corepressor).
• Activators stimulate gene expression. They interact with RNA polymerase at promoters, promoting transcription initiation. Activators bind DNA poorly unless bound to a ligand (inducer).

Sensing the Environment (Two-Component Systems)

• Sensor Kinase: Membrane-bound, detects environmental signals, and then phosphorylates a target protein. Has sensing and kinase domains.
• Response Regulator: Cytosolic protein activated by the sensor kinase. Binds DNA to stimulate or repress gene expression, and activity is controlled by covalent modifications (e.g., dephosphorylation by phosphatases).

The Lactose Operon

• Historical Significance: Monod, Jacob, and Lwoff discovered inducible and constitutive gene expression (e.g., in lactose and glucose metabolism) for which they were awarded the Nobel Prize.
• Lactose Metabolism (E. coli): Lactose is used as a carbon source. Required proteins are lactose permease (LacY) for transport and β-galactosidase (LacZ) for cleavage or rearrangement of lactose.

Regulation of the lac Operon

• Operon Structure: lacZ, lacY, and lacA form an operon, regulated by a single promoter and operator sequences.
• LacI Repressor: This gene is transcribed constitutively; the repressor (LacI) binds to the operator when lactose is absent, preventing transcription.
• Lactose Presence: Allolactose (formed from lactose) binds LacI, decreasing its affinity for the operator, allowing transcription initiation of lacZY A.

cAMP and CRP

• cAMP accumulation signals carbon starvation in the cell.
• cAMP binds to CRP (cAMP receptor protein).
• The cAMP-CRP complex interacts with RNA polymerase to activate transcription, increasing the lactose operon expression (necessary in the absence of glucose).

Catabolite Repression

• Catabolite repression occurs when a preferred nutrient (e.g., glucose) represses the expression of an operon for a less favorable nutrient (e.g., lactose).
• Diauxic growth: A biphasic growth curve when using two different carbon sources.
• Inducer exclusion: Glucose transport inhibits lactose permease (LacY), preventing lactose entry and lactose operon induction. Glucose transport is also modulated through phosphorylation (IIAGlc and IIBGlc) affecting LacY and triggering the operon.

Explore the intricate mechanisms of gene regulation in bacteria, focusing on transcriptional control. Learn how regulatory proteins interact with DNA to modulate gene expression and the role of repressors and activators. This quiz covers the essential concepts of gene regulation and its importance in cellular function.