1. more regulating gene expression

2. Combinations of 3 nucleotides code for each 1 amino acid in a protein. We looked at the mechanisms of gene expression, now we will look at its regulation.

3. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational Fig 15.1

4. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational Fig 15.1

5. Eukaryotic transcription must be activated by binding of transcription factors Fig 12.14

6. Mutations in the promoter show critical nucleotides

7. Enhancers are regulatory regions located some distance away from the promoter Fig 15.12

8. Proteins that help bend DNA can play an important role in transcription Fig 15.12

9. DNA bends to bring different areas in to close contact. Fig 15.12

10. How do eukaryotic cells jointly express several proteins (without operons)?

11. Promoter sequences where transcription factors can bind activating multiple gene in response to the environment

12. Promoters typically have several regulatory sequences Fig 12.13

13. Steroid response element

14. Steroids bind to receptors/transcription factors inside cell get translocated to the nucleus bind to promoters and activate transcription. cytoplasm Fig 15.6

15. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational Fig 15.1

16. Fig 23.25 Alternate Splicing in Drosophila Sex Determination

17. Alternate splicing leads to sex determination in fruit flies Fig 23.25

18. Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled Jennifer L. Chisa and David T. Burke Genetics, Vol. 175: 1079-1087, March 2007 Regulation of gene expression is often in response to a changing environment. But how stable can alternative splicing be, and does it play a role in maintaining homeostasis?

19. Alternative splicing modifies at least half of all primary mRNA transcripts in mammals. More than one alternative splice isoform can be maintained concurrently in the steady state mRNA pool of a single tissue or cell type, and changes in the ratios of isoforms have been associated with physiological variation and susceptibility to disease. Splice isoforms with opposing functions can be generated; for example, different isoforms of Bcl-x have pro-apoptotic and anti-apoptotic function. Chisa, J. L. et al. Genetics 2007;175:1079-1087 Fig. 1

20. Alternatively spliced versions of different genes were identified

21. Chisa, J. L. et al. Genetics 2007;175:1079-1087 Fig. 4 variation in splice-isoform ratios is conserved in two genetically diverse mouse populations Black= genetically heterogeneous population UMHET3 Red= a population of hybrid females

22. Chisa, J. L. et al. Genetics 2007;175:1079-1087 Fig. 5 In different individuals splice isoforms in different tissues are conserved

23. Conclusions: Alternate splicing for some genes is tightly regulated between different individuals. Slight differences in alternative splicing may be indicative of abnormalities (disease).

24. Molecular Biology of the Cell 4th ed. Alberts et al. Fig 6.40 http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.TOC&depth=2 mRNA transport is an important regulatory step

25. Molecular Biology of the Cell 4th ed. Alberts et al. Fig 7.52 http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.TOC&depth=2 mRNA can be localized to a specific parts of a cell (from Drosophila embryo)

26. Molecular Biology of the Cell 4th ed. Alberts et al. Fig 7.98 At least 3 mechanisms are involved: Directed transport via cytoskeleton Random diffusion and trapping Degradation and local protection

27. A processed mRNA ready for translation Protects from degradation/ recognition for ribosome Protects from degradation/ transport to cytoplasm 5’ untranslated region 3’ untranslated region

28. Molecular Biology of the Cell 4th ed. Alberts et al. Fig 7.99 http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.TOC&depth=2 mRNA with 3’ UTR properly localized mRNA without 3’ UTR improperly localized

29. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational Fig 15.1

30. Seeds germinated underground begin growing in darkness then emerge into light and begin photosynthesis energy from seed energy from sun

31. The level of this mRNA increases after plants are exposed to light. How might the cell accomplish this?

32. The level of this mRNA increases after plants are exposed to light. How might the cell accomplish this? Increased transcription and/or decreased mRNA degradation

33. Northern blot analysis: The level of this mRNA increases after plants are exposed to light. How might the cell accomplish this? Does this necessarily lead to increased protein production?

34. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational Fig 15.1

35. Fig 15.25 Regulation of iron assimilation in mammals: Regulating of Translation

36. Fig 15.26 Ferritin is regulated at translation

37. C. elegans is commonly used to study development

38. C. elegans development

39. C. elegans mutants with cells that do not develop properly.

40. The product of these genes was found to be RNA?

41. Cell vol. 116, 281-297 2004 MicroRNAs (miRNA) are ~22nt RNAs that play important regulatory roles

42. How do microRNAs control gene expression? miRNA expressed miRNA processed to ~22nt RNA Mature miRNA Fig 15.23 and

43. A processed mRNA ready for translation: microRNAs inhibit translation by binding to the 3’ end of mRNA microRNA bind to 3’-UTR 5’-UTR 3’-UTR

44. miRNA expressed miRNA processed to ~22nt RNA Mature miRNA the 3’ end with attached microRNA interacts with the 5’ end, blocking translation Fig 15.23 and

45. miRNAs can lead to methylation of DNA that leads to inhibition of transcription

46. microRNAs primarily target gene products that function during development Tbl 1

47. PNAS vol. 101 #1 pg 360-365, 2004 tissue specific expression of mouse microRNA

48. Silencing RNAs (siRNA) are artificially induced dsRNA Fig 15.21

49. siRNA with exact matches to the target mRNA causes degradation of the mRNA

50. microRNAsiRNA Translation inhibited mRNA degraded

51. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational

52. Phosphorylation and dephosphorylation of proteins can change activity

53. Ubiquitinization targets proteins for degradation

54. All protein interactions in an organism compose the interactome

55. Some proteins function in the cytoplasm; others need to be transported to various organelles.

56. How can proteins be delivered to their appropriate destinations?

57. Fig 13.23 Proteins are directed to their destinations via signals in the amino acid sequence

58. Protein Destinations: secretion or membrane

59. Signal sequences target proteins for secretion

60. Translation of secreted proteins

61. Translation of membrane bound proteins

62. Translation of secreted or membrane bound proteins This step determines secretion or membrane bound.

63. Protein Destinations: nucleus Signal anywhere in protein, Translation in cytoplasm, Signal not removed

64. Protein Destinations: mitochondria or chloroplast Signal translated first, Translation in cytoplasm, Signal removed

65. Protein Destinations: signals in protein determine destination Tbl 13.8

66. Development: differentiating cells to become an organism