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

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  • 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

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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

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  • 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

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  • 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

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

References

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