Regulation of Gene Expression

Regulation of Gene Expression

• Cells regulate gene expression in response to environmental changes
• Gene regulation is crucial for development and maintenance of different cell types in multicellular organisms

Orchestrating Gene Expression

• Cells intricately regulate gene expression in a way similar to an orchestra
• Both prokaryotes and eukaryotes alter gene expression patterns in response to environmental changes
• Multicellular eukaryotes develop and maintain multiple cell types
• Each cell type contains the same genome but expresses a different subset of genes

Precise Timing

• Gene expression is carefully regulated at every stage of development, ensuring genes are expressed at the right time and place
• Using mRNA techniques mRNA can be labeled different colors based on the gene

Bacterial Response to Environmental Change

• Bacteria respond to environmental change by regulating transcription
• Natural selection favors bacteria that express only necessary genes, conserving resources
• Bacterial cells conserve resources and energy, giving them a selective advantage

Metabolic Control in Bacteria

• Metabolic control occurs on two levels: adjusting enzyme activity and regulating enzyme production
• Cells adjust enzyme activity, a fast response relying on enzyme sensitivity to chemical cues
• Feedback inhibition rapidly regulates metabolic pathways

Enzyme Production Adjustment

• Cells adjust enzyme production levels by regulating the expression of enzyme-encoding genes
• When an environment provides enough tryptophan, the cell stops making tryptophan-synthesizing enzymes.
• Enzyme production control occurs at the transcriptional level, affecting messenger RNA synthesis
• Metabolic status changes switch numerous bacterial genes on or off

Operon Model

• Bacteria control gene expression using the operon model
• E. coli synthesizes tryptophan from a precursor molecule via a multi-step pathway
• Each reaction is catalyzed by a specific enzyme, with five genes coding for subunits clustered on the bacterial chromosome
• A single promoter serves all genes, forming a transcription unit
• Transcription gives rise to mRNA, coding for five polypeptides
• The mRNA translates into five polypeptides, punctuated by start and stop codons

Gene Grouping

• Grouping related function genes in a transcription unit allows a single "on-off switch" to control the whole cluster
• Genes are coordinately controlled
• A segment of DNA called an operator is the "on-off switch" in the bacterial genome
• Positioned within the promoter it controls RNA polymerase access to genes
• An operon comprises the operator, promoter, and genes they control, for enzyme production

Tryptophan Operon (trp)

• The trp operon (trp for tryptophan) is a key operon in the E. coli genome
• RNA polymerase can bind to the promoter and transcribe genes of the operon, turning the operon on
• Trp repressor switches the operon off
• It binds to the operator, preventing polymerase from attaching to the promoter

Repressor Proteins

• Repressor proteins are specific to the operator of a particular operon
• The trp repressor is the protein product of the regulatory gene called trpR
• Regulatory genes are expressed continuously, resulting in presence of some trp repressor molecules

Operator States

• An operator vacillates between two states: one bound to the repressor and one without it
• The number of active repressor molecules affects the relative duration of each state
• Trp repressor, like most regulatory proteins, is an allosteric protein with two alternative shapes, active and inactive
• It’s synthesized in an inactive form without affinity for operator

Tryptophan's Role

• Tryptophan functions as a corepressor by binding to the repressor protein
• The repressor protein changes to its active form; attaches to the operator, and turns off operon
• The trp operon responds to change in the cell's internal and external environment

Repressible vs Inducible Operons

• The trp operon is a repressible operon, usually on but can be repressed via a small molecule.
• An inducible operon is usually off but stimulation (induced) occurs following the interaction of the regulatory protein with a small molecule.