EM

Gene Expression Regulation in Eukaryotes

Regulation of Gene Expression in Eukaryotes

  • Eukaryotic gene expression is regulated at multiple levels: transcription, mRNA processing, translation, and post-translational modifications.

Transcriptional Regulation

  • Regulatory Transcription Factors:
    • Can activate or inhibit transcription.
    • Bind to specific DNA sequences, influencing gene expression.
  • Nucleosomes and Transcription:
    • The arrangement and composition of nucleosomes play critical roles in regulating transcription.
    • DNA Methylation:
    • Typically inhibits transcription when methyl groups are added to cytosine bases.
  • Insulators:
    • Sequences that confine gene regulation to specific regions, preventing unwanted interactions between enhancers and promoters.
  • Core Promoter:
    • Bound by transcription factors to recruit RNA polymerase (RNApol).
  • Enhancers/Silencers:
    • Enhancers are bound by activators to promote transcription while silencers are bound by repressors to inhibit transcription.

RNA Processing

  • Alternative Splicing:
    • Allows for the inclusion or exclusion of exons, leading to different mRNA products and protein diversity.
  • RNA Editing:
    • Modifies the base sequence of mRNAs before translation, affecting protein synthesis.

Translation Regulation

  • Small RNAs (miRNAs and siRNAs):
    • Silence translation of mRNA via RNA interference.
    • Their action can lead to degradation of target mRNAs.
  • mRNA Stability:
    • Influenced by RNA-binding proteins that stabilize or destabilize mRNA, affecting its lifespan.

Post-Translational Modifications

  • Covalent Modifications:
    • Include phosphorylation and acetylation, which regulate protein activity and functionality.
  • Feedback Inhibition:
    • A mechanism that regulates the activity of proteins based on the concentration of substrates/products.

Mechanisms of Gene Regulation

  • Histone Modifications:
    • Modifications of histone tails influence the structure of chromatin. Examples include:
    • Histone Acetylation: Typically associated with transcriptional activation.
    • Histone Deacetylation: Generally linked to transcriptional repression.
  • Nucleosome Positioning:
    • Nucleosomes are often positioned to create nucleosome-free regions (NFR) at transcription start and termination sites, facilitating the recruitment of transcriptional machinery.

Example: Sex Determination in Fruit Flies (Drosophila)

  • Sex Determination Mechanism:
    • XX diploid females express the sex-lethal gene (Sxl) from an early promoter, leading to female-specific splicing of tra and dsx mRNAs.
    • XY diploid males do not express Sxl, resulting in male-specific dsx splicing and gene expression.
    • Heterodimer vs. Homodimer Formation:
    • Different combinations of transcription factors (TFs) can alter promoter accessibility and gene activation.

Summary of Regulatory Mechanisms

  • Gene expression in eukaryotes is tightly regulated by various mechanisms at different stages:
    • At the transcriptional level through regulatory proteins and chromatin structure.
    • At the post-transcriptional level via splicing, stability, and small RNAs.
    • At the translational level by interaction of mRNA with proteins and small RNAs.
    • Lastly, post-translational modifications influence the function and lifespan of proteins.