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.