General Biology/Genetics/Gene Regulation

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• Not all genes are expressed in a cell
• Gene expression can be turned on and off
• Multiple levels of regulation gene function
  • Transcription initiation
• State of chromatin
• Transcription factors
  • Post-transcriptional
• mRNA processing
• mRNA half-life
• Translational
• Post-translational
  • Protein modification

Transcriptional control

• State of chromatin
  • Euchromatin: transcriptionally active
  • Heterochromatin: transcriptionally inactive
  • Chemical modification of histones
  • Methylation of bases
• Transcription factors
  • Bind to DNA at promoter or other regulatory sites (enhancers)
• Recognize base sequence through major and minor grooves
  • Recruit RNA polymerase

DNA grooves

Categories of transcription factors in eukaryotes

• Helix-turn-helix
  • Two small "-helices
  • Fit into DNA groove
• Homeodomain
  • Highly conserved helical domains
  • ~60 amino acids
• Zinc finger motif
  • Zn atom bound
• Leucine zipper
  • dimer

Regulatory proteins

• Activity may depend upon allosteric binding of small molecules
  • cAMP
  • Co-repressors
  • Inhibitors
• Binding to promoter region may “bend” DNA, making it accessible to other regulatory proteins

Lac operon of E. coli

• Single promoter region for cluster of genes
• Regulated and transcribed as a single unit
• Operons typical in prokaryotes
• Repressor: turns OFF gene expression

lac repressor

• Turns off transcription by blocking access by RNA polymerase
• repressor in activated by allosteric binding of lactose

Regulation in eukaryotes

• Both proximal (promoter) and distal (enhancer) to gene
• Typically transcription unit encodes a single polypeptide
• Promoter
  • TATA box
  • Other elements (regulatory sequences) may be present
• Enhancers
  • Work upstream, downstream, close, far from gene
  • Bend DNA

Alternative splicing

• Single transcript gives rise to 2 or more mature mRNAs
  • encode different polypeptides with shared domains
  • tissue and developmentally specific

References

This text is based on notes very generously donated by Paul Doerder, Ph.D., of the Cleveland State University.