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.