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Hoofdstuk 18 2008 deel 1 Hoofdstuk 18 2008 deel 1 Presentation Transcript

  • Chapter 18 Regulation of gene expression Groen: Brinker expression Rood: Knirps Blauw: Delta, vein marker From: Cook et al. 2004, Dev Biol. 131, 2113-2124
  • Contents Chapter 18
    • Regulation of gene expression
      • Control of bacterial gene expression
      • Control of eukaryotic gene expression
      • Noncoding RNAs
      • Cell differentiation is due to regulation of gene expression
      • Cancer is an example of deregulated gene expression
  • 2 Regulation of a metabolic pathway
    • Two levels
      • Enzyme level
        • Immediate
        • Feedback inhibition
        • Not further discussed in this chapter
      • Transcription, expression of genes
        • Operon model
        • Jacob and Monod
  • 2 Regulation of a metabolic pathway
    • Two levels
      • Enzyme level
        • Immediate
        • Feedback inhibition
        • Not further discussed in this chapter
      • Transcription, expression of genes
        • Operon model
        • Jacob and Monod
  • 3 The tryptophane or trp -operon
    • Operon contains multiple genes
      • involved in similar process
    • One long mRNA
      • multiple open reading frames
  • 3 The tryptophane or trp -operon
    • Operon contains multiple genes
      • involved in similar process
    • One long mRNA
      • multiple open reading frames
  • 3 The tryptophane or trp -operon
    • Operon contains multiple genes
      • involved in similar process
    • One long mRNA
      • multiple open reading frames
  • 3 Function of the repressor and operator
    • Absence of tryptophan  inactive repressor  RNA pol active
    • Presence of trp  binding to repressor  activation of repressor  blockade of RNA pol
  • Ways to control an operon
    • Repressible operon
      • Trp - and Lac - operon
      • Transcription is inhibited by binding of the regulatory protein
        • Activated by tryptophan, respectively lactose
    • Inducible operon
      • Lactose or lac -operon
      • Transcription is induced by transcription factor CAP
        • C atabolite a ctivator p rotein
    Cooper: The cell, 2 nd ed.
  • 4 The lac -operon without lactose
    • LacI , the repressor, coincidentally just upstream of operon
        • No lactose: no transcription of unwanted genes
  • 4 Lac operon switched on
    • Allolactose, isomer of lactose, binds repressor
      • Allolactose inactivates repressor
      • Activation of lac -operon genes
  • 5 Glucose is preferred
  • 5 Glucose is preferred
  • 5 Glucose is preferred
    • Lactose present but no glucose:
      • Activation of CAP
        • By cAMP
    • In presence of glucose
      • No cAMP and therefore inactive CAP
  • Outline
    • Bacteria
      • Control of gene expression
        • Tryp and LacZ
    • Eukaryotic gene expression
      • Complex and multi-level
      • Differential gene expression
      • Non-coding, regulatory RNA
      • Cancer
  • 6 Several controls in eukaryotic gene expression
    • From outside signal to changing gene expression
  • First way to control gene expression 7 Chromatin structure
    • Some covalent modifications of chromatin
      • Methylation
      • Phosphorylation
      • Acetylation
        • Opens up chromatin
        • Easier access for transcription machinery
  • First way to control gene expression 7 Chromatin structure
    • Some covalent modifications of chromatin
      • Methylation
      • Phosphorylation
      • Acetylation
        • Opens up chromatin
        • Easier access for transcription machinery
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  • 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
    • Tc terminates by PolyA sequence
    • AUG can be on 2 nd exon
    • Cap is added when RNA is about 20-30 nucleotides long
      • Not after polymerase termination
    • Three post- (or during-) transcriptional processing steps
    Thank you…
  • How does RNA polymerase find its start?
    • How is a gene found?
      • 25,000 genes in a sea of DNA
        • Less than 1% of DNA belongs to a gene
        • Transcription start signals are less than 1% of total DNA in a gene
          • Find a specific start basepair in 10,000 basepairs
  • 9 Role of enhancers and transcription factors
    • Enhancers are DNA sequences
    • Transcription factors are proteins!
      • Activator
      • Mediator
        • Multi-subunit complex
      • General Tc-factors
      • DNA-bending proteins)
    (
  • 9 Role of enhancers and transcription factors
    • Enhancers are DNA sequences
    • Transcription factors are proteins!
      • Activator
      • Mediator
        • Multi-subunit complex
      • General Tc-factors
      • DNA-bending proteins)
    (
  • 9 Role of enhancers and transcription factors
    • Enhancers are DNA sequences
    • Transcription factors are proteins!
      • Activator
      • Mediator
        • Multi-subunit complex
      • General Tc-factors
      • DNA-bending proteins)
    (