Gene Expression Control: Bacterial and Eukaryotic Regulation

Gene Regulation Characteristics

Introduction to Gene Regulation

Gene regulation refers to the mechanisms that control the expression of genes, ensuring that the correct genes are expressed at the proper times and in appropriate amounts. This process is essential for cellular function, development, and adaptation to environmental changes.

• Structural genes: Encode proteins that perform cellular functions.

• Regulatory genes: Encode products (often proteins) that interact with other sequences to affect transcription and translation.

• Regulatory elements: Non-transcribed DNA sequences that regulate other nucleotide sequences.

Types of Gene Expression

• Constitutive expression: Genes are continuously expressed under normal conditions.

• Positive control: Regulatory mechanisms that stimulate gene expression.

• Negative control: Regulatory mechanisms that inhibit gene expression.

Levels of Gene Regulation

Stages of Regulation

Gene expression can be regulated at multiple levels, from DNA structure to post-translational modification of proteins.

• Alteration of DNA structure (chromatin remodeling)

• Transcription (DNA to pre-mRNA)

• mRNA processing (splicing, capping, polyadenylation)

• mRNA stability and transport

• Translation (mRNA to protein)

• Post-translational modification (protein activation/inactivation)

Gene Regulation in Bacterial Cells

Operon Structure

An operon is a cluster of genes under the control of a single promoter and operator, allowing coordinated regulation of gene expression in prokaryotes.

• Promoter: DNA sequence where RNA polymerase binds to initiate transcription.

• Operator: DNA sequence where regulatory proteins bind to control transcription.

• Structural genes: Genes encoding enzymes or functional proteins.

• Regulator gene: Encodes a regulatory protein (repressor or activator).

Types of Operon Control

• Inducible operons: Transcription is usually off and must be turned on by an inducer.

• Repressible operons: Transcription is normally on and must be turned off by a repressor.

Negative Inducible Operons

• Regulator protein is an active repressor that binds the operator and inhibits transcription.

• An inducer molecule binds the repressor, inactivating it and allowing transcription.

Negative Repressible Operons

• Regulator protein is synthesized as an inactive repressor.

• A corepressor molecule binds the repressor, activating it to bind the operator and inhibit transcription.

Positive Inducible and Repressible Operons

• Positive inducible: Inactive activator becomes active upon binding an inducer, turning transcription on.

• Positive repressible: Active activator is inactivated by a product, turning transcription off.

Summary Table: Types of Operon Regulation

Type	Regulator Protein	Effector Molecule	Transcription State
Negative Inducible	Active repressor	Inducer inactivates repressor	Off (unless inducer present)
Negative Repressible	Inactive repressor	Corepressor activates repressor	On (unless corepressor present)
Positive Inducible	Inactive activator	Inducer activates activator	Off (unless inducer present)
Positive Repressible	Active activator	Product inactivates activator	On (unless product present)

The lac Operon of Escherichia coli

Overview and Structure

The lac operon is a classic example of a negative inducible operon, regulating lactose metabolism in E. coli.

• Inducer: Allolactose

• lacl: Repressor encoding gene

• lacP: Operon promoter

• lacO: Operon operator

Structural Genes

• lacZ: Encodes β-galactosidase (breaks down lactose)

• lacY: Encodes permease (transports lactose into cell)

• lacA: Encodes transacetylase

Regulation Mechanism

• In the absence of lactose, the repressor binds to the operator, blocking transcription.

• When lactose is present, allolactose binds the repressor, inactivating it and allowing transcription of the structural genes.

• Repression is never complete; a low level of transcription always occurs.

Lactose Metabolism Pathway

• Lactose enters the cell via permease.

• β-galactosidase converts lactose to glucose, galactose, and allolactose.

• Allolactose acts as the inducer for the operon.

Partial Diploids and Mutations

Jacob and Monod used partial diploids (merozygotes) to study the lac operon. Mutations can be:

• Cis-acting: Affect only genes on the same DNA molecule (e.g., operator, promoter).

• Trans-acting: Affect genes on other DNA molecules (e.g., regulatory gene encoding repressor).

Summary Table: lac Operon Components

Component	Function
lacl	Encodes repressor protein
lacP	Promoter for RNA polymerase binding
lacO	Operator for repressor binding
lacZ	Encodes β-galactosidase
lacY	Encodes permease
lacA	Encodes transacetylase

Gene Regulation in Eukaryotes

Transcriptional Regulation

Eukaryotic gene regulation is more complex, involving multiple levels and regulatory elements.

• Basal transcription apparatus: Includes general transcription factors and RNA polymerase, required for minimal transcription.

• Transcription regulator proteins: Activators and repressors bind to regulatory promoters, enhancers, or silencers to modulate transcription.

• Enhancers and silencers: DNA sequences located away from the gene, bound by regulatory proteins to increase or decrease transcription.

• Insulators: DNA sequences that block the effect of enhancers on a gene.

Coordinated Gene Regulation

• Multiple genes can be regulated together by shared regulatory sequences or transcription factors.

Epigenetic Gene Regulation

Epigenetic Effects

Epigenetic regulation involves heritable changes in gene expression that do not alter the DNA sequence.

• DNA methylation: Addition of methyl groups to cytosine bases, often silencing gene expression.

• Histone modification: Post-translational modifications (e.g., methylation, acetylation, phosphorylation) of histone proteins affect chromatin structure and gene accessibility.

• Chromatin remodeling: Changes in chromatin structure can activate or repress gene expression.

Summary

• Operon structure and types of regulation (inducible/repressible, positive/negative)

• lac operon as a model for negative inducible regulation

• Mutational analysis reveals cis- and trans-acting elements

• Eukaryotic gene regulation involves complex interactions of regulatory proteins and DNA elements

• Epigenetic mechanisms provide additional layers of gene expression control