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Genomics of Transcriptional Regulation

Genomics of Transcriptional Regulation. Ken Daigoro Yokoyama Pollock lab. Why study regulation?. Directs complex processes Cross-species differences Not well understood. Overview. Promoter architecture Cis-regulatory element discovery Gene networks. Transcription.

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Genomics of Transcriptional Regulation

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  1. Genomics ofTranscriptional Regulation • Ken Daigoro Yokoyama • Pollock lab

  2. Why study regulation? • Directs complex processes • Cross-species differences • Not well understood

  3. Overview • Promoter architecture • Cis-regulatory element discovery • Gene networks

  4. Transcription

  5. Promoter architecture • Core promoter elements • Proximal promoter elements • Regulatory modules • Enhancers / Silencers

  6. TATAAA

  7. TATAAA

  8. TATAAA

  9. TATA-box

  10. Inr sequence

  11. Promoter elements TATA Upstream elements Inr Downstream elements

  12. GC box

  13. Broad vs Single peakPromoters Single peak

  14. Broad vs Single peakPromoters Single peak Broad peak

  15. Regulatory modules

  16. Do spatial preferences exist between motifs?

  17. Dinucleotide composition GC AT

  18. Functional motif discovery • Functional elements : ~20% noncoding DNA • Typically short : 6-12 bp • Degenerate sites

  19. Position weight matrices (PWMs) A C G T G/C T A T A A/T A A/T

  20. De novoMotif prediction • Input : Small set of promoters • Coregulation = Cooccurrence • Several user-defined parameters

  21. De novo Motif prediction

  22. De novo Motif prediction

  23. How accurate??

  24. Phylogenetic footprinting • Cross-species comparisons • Alignment-based • Highly conserved sequence elements

  25. Phylogenetic footprinting Human Macaque Mouse Rat Dog Cow Dodo Bird GWBush Frog Fish

  26. Regulatory element turnover

  27. Regulatory element turnover

  28. Regulatory element turnover

  29. Regulatory element turnover

  30. Promoter evolution • Sequence conservation vs Regulation • Alignments • Consensus sequence evolution

  31. Gene networks • Development, Differentiation, Apoptosis, Cancer progression • Complex relationships • Protein-protein-DNA interactions

  32. Gene networks

  33. Gene networks A B C

  34. Gene networks

  35. Transcriptional activation A B

  36. Transcriptional activation A B AND

  37. Transcriptional activation A B AND A B OR

  38. Transcriptional activation A B AND ON / OFF (Continuous) A B A B OR

  39. Transcriptional repression A B C

  40. Transcriptional repression A B C C

  41. Transcriptional repression A B C C

  42. Transcriptional repression A B C A B

  43. Transcriptional repression A B C A C B

  44. Transcriptional repression A B C A B B C

  45. Transcriptional repression A B C A B B C

  46. Transcriptional repression A B C A B C

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