Gene Expression

Cell & Molecular Biology Overview

  • Subject: Regulation of Gene Expression

  • Institution: TY-OF-C, SLU

Transmission of Traits

  • Mutation occurred ~7500 years ago allowing adults to express lactase enzyme into adulthood.

    • Enables digestion of milk, advantageous for those with domesticated mammals.

    • Referenced in upcoming Homework assignments.

Gene Expression

  • Natural selection favors bacteria that express only necessary genes.

  • Regulation methods:

    • Feedback Inhibition: End product of metabolic pathways inhibits enzyme production by blocking activity.

    • Gene Regulation: Adjusts enzyme production by regulating gene expression, primarily at transcription level.

  • Basic mechanism of gene regulation: Operon Model.

Operons

Definition

  • Cluster of functionally related genes controlled by an "on-off switch" (operator).

  • Entire DNA stretch includes operator, promoter, and controlled genes.

Functionality

  • Operon can be switched off by a repressor protein.

    • Repressor binds operator, blocking RNA polymerase and transcription.

    • It is the product of a separate regulatory gene.

Activation/Inactivation

  • Repressor can be active/inactive depending on other molecules (e.g. corepressor).

    • Example: E. coli synthesizes tryptophan when levels are low.

Tryptophan Operon (trp Operon)

  • Default state: ON, genes for tryptophan synthesis are transcribed.

  • When tryptophan is present, it binds to the repressor, turning the operon OFF.

  • Activation state of repressor depends on tryptophan levels.

Operon Types

Repressible Operon

  • Generally ON; repressor binding shuts off transcription.

    • Example: trp operon.

Inducible Operon

  • Generally OFF; inducer inactivates the repressor to activate transcription.

    • Example: Lac operon, regulating lactose metabolism.

Lac Operon

  • Includes genes for lactose hydrolysis and metabolism, controlled by lacI regulatory gene.

  • Lac repressor is active alone, turning off the operon.

  • Inducer: Allolactose, which inhibits repressor binding.

Positive Control of Operons

  • Some operons (e.g. lac operon) regulated by stimulatory proteins like CRP (cyclic AMP receptor protein).

  • Under low glucose, CRP binds cAMP activating transcription by enhancing RNA polymerase affinity.

  • Without CRP, transcription is normal/low when glucose is abundant.

Eukaryotic Gene Expression

  • All organisms regulate gene expression based on internal/external signals.

    • Essential for cell specialization in multicellular organisms.

    • Differential gene expression leads to cell-type differences, even with identical genomes.

    • Abnormalities may lead to diseases like cancer.

Chromatin's Role in Gene Expression

  • Chromatin structure influences gene expression:

    • Genes in heterochromatin generally not expressed.

    • Euchromatin expression affected by nucleosome location.

    • Chemical modifications of histones can alter expression.

Histone Modification

  • Histone Acetylation: Opens chromatin for transcription initiation.

  • Methylation: Can condense chromatin and reduce transcription.

DNA Methylation

  • Addition of methyl groups reduces transcription

    • Long-term gene inactivation in cellular differentiation.

    • Genomic imprinting regulates allele expression during development.

Control Mechanisms in Eukaryotic Gene Expression

  • Chromatin-modifying enzymes control the DNA binding capability of transcription machinery.

  • Control elements (noncoding DNA) serve as transcription factor binding sites.

Transcription Factors

  • General transcription factors are essential for protein-coding gene transcription.

  • Specific transcription factors required for certain genes, bind control elements (enhancers).

  • RNA polymerase II initiation requires a complete complex assembly.

Epigenetics

  • Involves multiple transcription factors determining transcription rate.

  • Differential Gene Expression: explains cell fate despite genomic equivalence.

  • Epigenetics: Study of gene expression changes without sequence alterations; reversible, sometimes stable, and heritable.

Inheritance Mechanism

  • Chromatin modifications can pass through generations.

  • Traits inherited via mechanisms not directly involving DNA sequence termed epigenetic inheritance.