4-3_-_Transcriptional_regulation

4-3: Transcriptional Regulation Lecture Overview

• Regulation of Transcription: Focus on transcriptional initiation in bacteria.

• Key Components: DNA-binding regulatory proteins, two-component regulatory systems, signaling molecules, quorum sensing.

• Textbook Reference: Chapter 7, parts I - III.

How to Regulate Gene Expression

• Importance of Regulation: Essential for cells to adapt to their environments by controlling gene activity.

• Examples:

  • Enzyme for arginine synthesis is regulated based on availability to avoid resource waste.

• Methods of Regulation:

  • Transcription (initiation), Translation (initiation, RNA turnover), Protein levels (degradation), Protein activity (modifications).

Transcriptional Initiation

• Common Regulation Method: Control of RNA polymerase binding to the promoter.

• Role of Transcription Factors: DNA-binding proteins help regulate RNA polymerase activity.

• Sensing Cues: Cells need to detect environmental signals to regulate gene expression effectively.

• Focus on Prokaryotes: Lecture primarily covers regulation in bacteria.

DNA-Binding Regulatory Proteins

• Function: Many regulatory proteins are DNA-binding and recognize specific DNA sequences.

• Domains: Bind DNA in the major groove and have additional domains for protein interactions and regulatory functions.

• Consensus Sequences: Recognition involves flexible sequence elements, often with repeats bound by homodimers.

Activators and Repressors

• Activator Function: Promote transcription by recruiting RNA polymerase; genes are under positive control.

• Repressor Function: Inhibit transcription by blocking RNAP binding; genes are under negative control.

• Dual Role: Some transcription factors can act as both activators and repressors depending on the gene.

Allosteric Regulatory Proteins

• Mechanism: Regulated by small molecules that activate or deactivate binding to DNA.

• Inducers and Corepressors:

  • Inducers activate and allow transcription; corepressors inhibit gene expression.

• System Types:

  • Inducible systems are normally off and can be turned on.

  • Repressible systems are normally on and can be turned off.

Example of Repressible System: Arginine Biosynthesis

• ArgR Protein: Acts as a repressor for arginine biosynthesis operon, regulating expression based on arginine levels.

• Mechanism:

  • Low arginine allows gene expression; high arginine binds to ArgR and inhibits transcription.

The Lac Operon

• Importance: Enables E. coli to use lactose when available and is regulated by the LacI repressor.

• Induction Mechanism: Allolactose binds LacI, inactivating it and allowing transcription when lactose is present.

• Glucose Influence:

  • Low glucose elevates cAMP necessary for lac operon expression, demonstrating catabolite repression.

cAMP: A Signaling Molecule

• Definition: Cyclic AMP (cAMP) acts as a second messenger regulating various processes in bacteria.

• Production and Function: Generated in response to signals, influencing regulatory proteins during environmental changes.

Quorum Sensing

• Mechanism: Cells use signaling molecules called autoinducers to monitor local density and coordinate behaviors.

• Functionality: Activates group behaviors such as biofilm formation when cell density is high.

• Diversity of Signaling: Different types of autoinducers exist, with acyl homoserine lactones common in Gram-negative bacteria.

Quorum Sensing Dynamics

• Gene Regulation: Genes can be induced or repressed based on autoinducer concentrations; specific variations exist among species.

• Discovery: Initially identified in Vibrio fischeri, responsible for luminescence at high cell concentrations.

Two-Component Regulatory Systems

• Description: Utilize two proteins (sensor kinase and response regulator) for signal transduction in bacteria.

• Functionality: Sensor kinases detect signals and activate response regulators, which regulate gene expression.

• Prevalence: Many two-component systems exist; often tightly regulated with several layers of control.

Transcriptional Regulation in Archaea

• Comparison with Bacteria: While mechanisms differ, regulatory systems show similarities, especially in activator/repressor functions.

• Role of Two-Component Systems: Present but less common than in bacteria; eukaryotic systems are more complex.