Hoofdstuk 18 2008 deel 2

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Hoofdstuk 18 2008 deel 2

  1. 1. 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>(
  2. 2. 10 Transcription can make cells different (One of the most important concepts in biology !!!!)
  3. 3. 10 Transcription can make cells different (One of the most important concepts in biology !!!!)
  4. 4. 10 Transcription can make cells different (One of the most important concepts in biology !!!!) <ul><li>Note that a Tc-factor may be shared </li></ul>
  5. 5. 10 Transcription can make cells different (One of the most important concepts in biology !!!!) Concept question: how would the DNA sequence of an enhancer in a liver cell compare with that in a lens cell? <ul><li>Note that a Tc-factor may be shared </li></ul>
  6. 6. 11 Alternative splicing A third way for differential gene expression <ul><li>One gene, two transcripts </li></ul>
  7. 7. 12 P rotein degradation A 4th way to control gene expression <ul><li>Cells and their contents are constantly renewed and recycled </li></ul><ul><li>Half life different for different proteins </li></ul>
  8. 8. 13 Regulation by small RNAs ‘RNA interference’ <ul><li>miRNA: microRNAs </li></ul><ul><ul><li>21 bp </li></ul></ul><ul><li>Dicer </li></ul><ul><li>Two options </li></ul><ul><ul><li>Degradation </li></ul></ul><ul><ul><li>Translation block </li></ul></ul><ul><li>siRNA </li></ul><ul><ul><li>Small interfering RNA </li></ul></ul><ul><ul><li>From longer precursors </li></ul></ul><ul><ul><ul><li>Not necessarily from inside the cell </li></ul></ul></ul>
  9. 9. 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>Non-coding, regulatory RNA </li></ul></ul><ul><ul><li>Differential gene expression responsible for differential cell types </li></ul></ul><ul><ul><li>Cancer </li></ul></ul>
  10. 10. 14 From egg to tadpole <ul><li>A program of cell proliferation, differentiation, migration, morphogenesis </li></ul><ul><ul><li>(‘3-dimensional movement to create form’) </li></ul></ul><ul><li>How do cells become different? </li></ul>
  11. 11. 15 Cytoplasmic determinants and outside signals <ul><li>From within: cytoplasmic determinants </li></ul><ul><ul><li>Maternal products </li></ul></ul><ul><li>From outside: induction </li></ul><ul><ul><li>Signal transduction </li></ul></ul>
  12. 12. 16 Determination and differentiation of muscle cells
  13. 13. 16 Determination and differentiation of muscle cells
  14. 14. 16 Determination and differentiation of muscle cells
  15. 15. 17 Developmental events in the life cycle of Drosophila
  16. 16. 18 Something went wrong: A homeotic transformation <ul><li>Mutation in a homeotic gene </li></ul><ul><ul><li>The antennapedia gene complex </li></ul></ul>
  17. 17. 19 The two-tailed fly: bicoid <ul><li>Nüsslein-Volhard </li></ul>
  18. 18. 19 The two-tailed fly: bicoid <ul><li>Nüsslein-Volhard </li></ul>
  19. 19. 19 The two-tailed fly: bicoid <ul><li>Nüsslein-Volhard </li></ul>
  20. 20. Outline Chapter 18 <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>Non-coding, regulatory RNA </li></ul></ul><ul><ul><li>Differential gene expression responsible for differential cell types </li></ul></ul><ul><ul><li>Cancer </li></ul></ul>
  21. 21. 20 From proto-oncogen to oncogen <ul><li>Three (or four) ways to become an oncogene </li></ul>
  22. 22. 21 Signaling pathways for cell division Stimulatory pathway
  23. 23. 21 Signaling pathways for cell division Inhibitory pathway
  24. 24. 21 Signaling pathways for cell division Inhibitory pathway
  25. 25. 22 Model for development of colon cancer
  26. 26. BRCA1 and BRCA2 tumor suppressors of breast tumors <ul><li>Haploinsufficiency </li></ul><ul><ul><li>One allele of wildtype BRCA1 </li></ul></ul><ul><ul><ul><li>Chance on breast tumor 30-fold increased </li></ul></ul></ul><ul><li>BRCA genes involved in DNA repair </li></ul><ul><ul><li>Tumour suppressors </li></ul></ul>Mary-Claire King
  27. 27. Bacterial summary <ul><li>Bacteria change gene expression by regulating transcription </li></ul><ul><ul><li>Lac and Trp operon </li></ul></ul>
  28. 28. Eukaryotic summary <ul><li>Eukaryotic gene expression regulated at many levels </li></ul><ul><ul><li>Chromatin modifications </li></ul></ul><ul><ul><li>Non-coding RNAs </li></ul></ul><ul><ul><li>Processing </li></ul></ul><ul><ul><ul><li>Splicing </li></ul></ul></ul><ul><ul><li>Transcription </li></ul></ul><ul><ul><ul><li>Role of enhancers </li></ul></ul></ul><ul><ul><ul><li>Loop model </li></ul></ul></ul><ul><ul><ul><li>Cell specificity of activators </li></ul></ul></ul><ul><ul><li>Protein degradation </li></ul></ul><ul><li>Development </li></ul><ul><li>Cancer </li></ul><ul><ul><li>Oncogenes and tumour suppressors </li></ul></ul>

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