Regulation of Gene Expression Lecture

Introduction

• Focus on how cells regulate gene expression
• Importance of previous knowledge on transcription and translation

Central Dogma Recap

• Transcription: DNA codes for mRNA
  • Post-transcriptional modifications: 5' cap, poly-A tail
  • Spliceosome removes introns, joins exons
  • mRNA moves to cytoplasm
• Translation: mRNA, ribosome, tRNAs produce polypeptides
  • Folding and modification in ER and Golgi apparatus

Regulatory Mechanisms

• Cells have same genes but express differently based on purpose (muscle, nerve, liver cells)

Bacterial Gene Regulation

• Operons: Key in bacterial gene regulation
  • Example: E. coli operon for tryptophan production
  • Operons include a promoter, operator, and genes
  • Repressor Proteins: Bind to operators to block transcription
    • Example: Tryptophan repressor activated by tryptophan binding

Negative vs. Positive Gene Regulation

• Negative Regulation:
  • Genes typically on unless repressed
  • Example: Lactose metabolism in E. coli (allolactose deactivates repressor)
• Positive Regulation:
  • Signaling molecules increase RNA polymerase affinity for promoters
  • Example: c-AMP as an activator

Eukaryotic Gene Expression

• Histone Modification:
  • Acetylation, methylation, phosphorylation alter DNA binding
  • More accessible DNA can be transcribed
• Transcription Factors:
  • Bind to promoters (e.g., TATA box) to enhance transcription
  • Activation and binding domains help assemble transcription complex
• Enhancers and Activators:
  • Enhancers far from gene interact with activators to facilitate transcription
• Hormonal Influence:
  • Hormones can trigger gene expression during development (e.g., puberty)

Complex Regulation

• Combination of acetylation, mRNA binding, and other mechanisms
• Small number of inputs can regulate thousands of genes

Conclusion

• Understanding regulatory mechanisms prepares us for more complex biological systems.