Eukaryotic Gene Regulation

Importance of Gene Regulation

• Eukaryotic organisms adapt to environmental changes through gene regulation.
• Gene expression is tightly controlled during the cell cycle, ensuring only necessary proteins are produced.
• In multicellular organisms, it defines distinct tissues and cellular functions.

Mechanisms of Gene Regulation

• Occurs at multiple stages: transcription, RNA processing, translation, and post-translational modification.
• Regulatory transcription factors (RTFs) regulate transcription; general transcription factors (GTFs) are essential for basal transcription.

Types of Transcription Factors

• General Transcription Factors (GTFs): Bind RNA polymerase to core promoter.
• Regulatory Transcription Factors (RTFs): Modulate transcription rates for specific genes.

Mechanisms of Action

• RTFs bind to regulatory sequences affecting transcription.
• Activators: Bind to enhancers; increase transcription rates significantly.
• Repressors: Bind to silencers; decrease transcription rates.
• Key protein complexes include TFIID (binds TATA box) and Mediator (transitions from initiation to elongation).

Combinatorial Control of Gene Expression

• Involves small effector molecules, protein interactions, DNA methylation, and nucleosome alterations.
• Example: Glucocorticoid receptors influence nutrient metabolism.

Chromatin Remodeling and Histone Modifications

• Chromatin Structure: Altered by ATP-dependent complexes, affecting transcription factor access.
• Histone Code: Refers to modifications (acetylation, methylation) regulating transcription.

Nucleosome Positioning

• Eukaryotic genes have characteristic nucleosome organization essential for transcription.
• Active genes have a nucleosome-free region (NFR) around the core promoter.

DNA Methylation

• Primarily by DNA methyltransferase; silences gene expression.
• CpG Islands: Crucial for regulation near promoters; their methylation status influences transcription.

Epigenetic Regulation

• Epigenetics: Heritable changes in gene expression without DNA sequence alteration; includes:
  • DNA methylation
  • Chromatin remodeling
  • Histone modifications
• Feedback loops enhance gene expression.

Environmental Influences on Epigenetics

• Environmental agents (temperature, diet, toxins) can induce epigenetic changes.

Heterochromatin vs. Euchromatin

• Euchromatin: Less compact; actively transcribed.
• Heterochromatin: Tightly packed; transcriptionally inactive; involved in gene silencing and maintaining genomic stability.

Regulation of Translation and Iron Assimilation

• RNA-binding proteins control mRNA stability and translation.
• Iron Regulatory Proteins (IRPs) modulate mRNA dependent on cellular iron levels.