Chapter 18 Regulation of gene expression Groen: Brinker expression Rood:  Knirps Blauw: Delta, vein marker From: Cook et a...
Contents Chapter 18 <ul><li>Regulation of gene expression </li></ul><ul><ul><li>Control of bacterial gene  expression </li...
2  Regulation of a metabolic pathway <ul><li>Two levels </li></ul><ul><ul><li>Enzyme level </li></ul></ul><ul><ul><ul><li>...
2  Regulation of a metabolic pathway <ul><li>Two levels </li></ul><ul><ul><li>Enzyme level </li></ul></ul><ul><ul><ul><li>...
3  The tryptophane or trp -operon <ul><li>Operon contains multiple genes </li></ul><ul><ul><li>involved in similar process...
3  The tryptophane or trp -operon <ul><li>Operon contains multiple genes </li></ul><ul><ul><li>involved in similar process...
3  The tryptophane or trp -operon <ul><li>Operon contains multiple genes </li></ul><ul><ul><li>involved in similar process...
3  Function of the repressor and operator <ul><li>Absence of tryptophan   inactive repressor   RNA pol active </li></ul>...
Ways to control an operon <ul><li>Repressible operon </li></ul><ul><ul><li>Trp - and  Lac - operon </li></ul></ul><ul><ul>...
4  The  lac -operon without lactose <ul><li>LacI , the repressor, coincidentally just upstream of operon </li></ul><ul><ul...
4   Lac  operon switched on <ul><li>Allolactose, isomer of lactose, binds repressor </li></ul><ul><ul><li>Allolactose inac...
5  Glucose is preferred
5  Glucose is preferred
5  Glucose is preferred <ul><li>Lactose present but no glucose: </li></ul><ul><ul><li>Activation of CAP </li></ul></ul><ul...
Outline <ul><li>Bacteria </li></ul><ul><ul><li>Control of gene expression </li></ul></ul><ul><ul><ul><li>Tryp and LacZ </l...
6  Several controls in  eukaryotic gene expression <ul><li>From outside signal to changing gene expression </li></ul>
First way to control gene expression   7 Chromatin structure <ul><li>Some covalent modifications of chromatin </li></ul><u...
First way to control gene expression   7 Chromatin structure <ul><li>Some covalent modifications of chromatin </li></ul><u...
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) <ul><li>Tc terminates by PolyA sequence </li></ul>...
How does RNA polymerase find its start? <ul><li>How is a gene found? </li></ul><ul><ul><li>25,000 genes in a sea of DNA </...
9  Role of enhancers and transcription factors <ul><li>Enhancers are DNA sequences </li></ul><ul><li>Transcription  factor...
9  Role of enhancers and transcription factors <ul><li>Enhancers are DNA sequences </li></ul><ul><li>Transcription  factor...
9  Role of enhancers and transcription factors <ul><li>Enhancers are DNA sequences </li></ul><ul><li>Transcription  factor...
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Hoofdstuk 18 2008 deel 1

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Transcript of "Hoofdstuk 18 2008 deel 1"

  1. 1. 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
  2. 2. Contents Chapter 18 <ul><li>Regulation of gene expression </li></ul><ul><ul><li>Control of bacterial gene expression </li></ul></ul><ul><ul><li>Control of eukaryotic gene expression </li></ul></ul><ul><ul><li>Noncoding RNAs </li></ul></ul><ul><ul><li>Cell differentiation is due to regulation of gene expression </li></ul></ul><ul><ul><li>Cancer is an example of deregulated gene expression </li></ul></ul>
  3. 3. 2 Regulation of a metabolic pathway <ul><li>Two levels </li></ul><ul><ul><li>Enzyme level </li></ul></ul><ul><ul><ul><li>Immediate </li></ul></ul></ul><ul><ul><ul><li>Feedback inhibition </li></ul></ul></ul><ul><ul><ul><li>Not further discussed in this chapter </li></ul></ul></ul><ul><ul><li>Transcription, expression of genes </li></ul></ul><ul><ul><ul><li>Operon model </li></ul></ul></ul><ul><ul><ul><li>Jacob and Monod </li></ul></ul></ul>
  4. 4. 2 Regulation of a metabolic pathway <ul><li>Two levels </li></ul><ul><ul><li>Enzyme level </li></ul></ul><ul><ul><ul><li>Immediate </li></ul></ul></ul><ul><ul><ul><li>Feedback inhibition </li></ul></ul></ul><ul><ul><ul><li>Not further discussed in this chapter </li></ul></ul></ul><ul><ul><li>Transcription, expression of genes </li></ul></ul><ul><ul><ul><li>Operon model </li></ul></ul></ul><ul><ul><ul><li>Jacob and Monod </li></ul></ul></ul>
  5. 5. 3 The tryptophane or trp -operon <ul><li>Operon contains multiple genes </li></ul><ul><ul><li>involved in similar process </li></ul></ul><ul><li>One long mRNA </li></ul><ul><ul><li>multiple open reading frames </li></ul></ul>
  6. 6. 3 The tryptophane or trp -operon <ul><li>Operon contains multiple genes </li></ul><ul><ul><li>involved in similar process </li></ul></ul><ul><li>One long mRNA </li></ul><ul><ul><li>multiple open reading frames </li></ul></ul>
  7. 7. 3 The tryptophane or trp -operon <ul><li>Operon contains multiple genes </li></ul><ul><ul><li>involved in similar process </li></ul></ul><ul><li>One long mRNA </li></ul><ul><ul><li>multiple open reading frames </li></ul></ul>
  8. 8. 3 Function of the repressor and operator <ul><li>Absence of tryptophan  inactive repressor  RNA pol active </li></ul><ul><li>Presence of trp  binding to repressor  activation of repressor  blockade of RNA pol </li></ul>
  9. 9. Ways to control an operon <ul><li>Repressible operon </li></ul><ul><ul><li>Trp - and Lac - operon </li></ul></ul><ul><ul><li>Transcription is inhibited by binding of the regulatory protein </li></ul></ul><ul><ul><ul><li>Activated by tryptophan, respectively lactose </li></ul></ul></ul><ul><li>Inducible operon </li></ul><ul><ul><li>Lactose or lac -operon </li></ul></ul><ul><ul><li>Transcription is induced by transcription factor CAP </li></ul></ul><ul><ul><ul><li>C atabolite a ctivator p rotein </li></ul></ul></ul>Cooper: The cell, 2 nd ed.
  10. 10. 4 The lac -operon without lactose <ul><li>LacI , the repressor, coincidentally just upstream of operon </li></ul><ul><ul><ul><li>No lactose: no transcription of unwanted genes </li></ul></ul></ul>
  11. 11. 4 Lac operon switched on <ul><li>Allolactose, isomer of lactose, binds repressor </li></ul><ul><ul><li>Allolactose inactivates repressor </li></ul></ul><ul><ul><li>Activation of lac -operon genes </li></ul></ul>
  12. 12. 5 Glucose is preferred
  13. 13. 5 Glucose is preferred
  14. 14. 5 Glucose is preferred <ul><li>Lactose present but no glucose: </li></ul><ul><ul><li>Activation of CAP </li></ul></ul><ul><ul><ul><li>By cAMP </li></ul></ul></ul><ul><li>In presence of glucose </li></ul><ul><ul><li>No cAMP and therefore inactive CAP </li></ul></ul>
  15. 15. Outline <ul><li>Bacteria </li></ul><ul><ul><li>Control of gene expression </li></ul></ul><ul><ul><ul><li>Tryp and LacZ </li></ul></ul></ul><ul><li>Eukaryotic gene expression </li></ul><ul><ul><li>Complex and multi-level </li></ul></ul><ul><ul><li>Differential gene expression </li></ul></ul><ul><ul><li>Non-coding, regulatory RNA </li></ul></ul><ul><ul><li>Cancer </li></ul></ul>
  16. 16. 6 Several controls in eukaryotic gene expression <ul><li>From outside signal to changing gene expression </li></ul>
  17. 17. First way to control gene expression 7 Chromatin structure <ul><li>Some covalent modifications of chromatin </li></ul><ul><ul><li>Methylation </li></ul></ul><ul><ul><li>Phosphorylation </li></ul></ul><ul><ul><li>Acetylation </li></ul></ul><ul><ul><ul><li>Opens up chromatin </li></ul></ul></ul><ul><ul><ul><li>Easier access for transcription machinery </li></ul></ul></ul>
  18. 18. First way to control gene expression 7 Chromatin structure <ul><li>Some covalent modifications of chromatin </li></ul><ul><ul><li>Methylation </li></ul></ul><ul><ul><li>Phosphorylation </li></ul></ul><ul><ul><li>Acetylation </li></ul></ul><ul><ul><ul><li>Opens up chromatin </li></ul></ul></ul><ul><ul><ul><li>Easier access for transcription machinery </li></ul></ul></ul>
  19. 19. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  20. 20. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  21. 21. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  22. 22. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  23. 23. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  24. 24. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  25. 25. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA)
  26. 26. 8 Birth of a eukaryotic transcript (in this case a precursor for mRNA) <ul><li>Tc terminates by PolyA sequence </li></ul><ul><li>AUG can be on 2 nd exon </li></ul><ul><li>Cap is added when RNA is about 20-30 nucleotides long </li></ul><ul><ul><li>Not after polymerase termination </li></ul></ul><ul><li>Three post- (or during-) transcriptional processing steps </li></ul>Thank you…
  27. 27. How does RNA polymerase find its start? <ul><li>How is a gene found? </li></ul><ul><ul><li>25,000 genes in a sea of DNA </li></ul></ul><ul><ul><ul><li>Less than 1% of DNA belongs to a gene </li></ul></ul></ul><ul><ul><ul><li>Transcription start signals are less than 1% of total DNA in a gene </li></ul></ul></ul><ul><ul><ul><ul><li>Find a specific start basepair in 10,000 basepairs </li></ul></ul></ul></ul>
  28. 28. 9 Role of enhancers and transcription factors <ul><li>Enhancers are DNA sequences </li></ul><ul><li>Transcription factors are proteins! </li></ul><ul><ul><li>Activator </li></ul></ul><ul><ul><li>Mediator </li></ul></ul><ul><ul><ul><li>Multi-subunit complex </li></ul></ul></ul><ul><ul><li>General Tc-factors </li></ul></ul><ul><ul><li>DNA-bending proteins) </li></ul></ul>(
  29. 29. 9 Role of enhancers and transcription factors <ul><li>Enhancers are DNA sequences </li></ul><ul><li>Transcription factors are proteins! </li></ul><ul><ul><li>Activator </li></ul></ul><ul><ul><li>Mediator </li></ul></ul><ul><ul><ul><li>Multi-subunit complex </li></ul></ul></ul><ul><ul><li>General Tc-factors </li></ul></ul><ul><ul><li>DNA-bending proteins) </li></ul></ul>(
  30. 30. 9 Role of enhancers and transcription factors <ul><li>Enhancers are DNA sequences </li></ul><ul><li>Transcription factors are proteins! </li></ul><ul><ul><li>Activator </li></ul></ul><ul><ul><li>Mediator </li></ul></ul><ul><ul><ul><li>Multi-subunit complex </li></ul></ul></ul><ul><ul><li>General Tc-factors </li></ul></ul><ul><ul><li>DNA-bending proteins) </li></ul></ul>(

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