Chapter 2. Differential gene expression in Development

1. Chapter 2. Differential gene expression in Development Based on the basic assumtion, “Genomic equivalence”, scientist have asked “ how nuclear genes can direct development when these genes are exactly the same in every cell type?” • The answers are • Differentail gene expression • Selective nuclear RNA processing • Selective messenger RNA translation • Differential protein modification

2. Figure 2.1 Cloning a mammal using nuclei from adult somatic cells Evidence for genetic equivalence -Nuclear transfer and cloning of frog(1952, Briggs and King) -Nuclear transfer from adult frog(1975, Gurdon et al.) -Nuclear transfer in sheep(1997, Wilmut)

3. Figure 2.2 The kitten “CC” (From 9th Edition) Resurrection is not possible!

4. Figure 2.2 Nucleosome and chromatin structure

5. Figure 2.2 Nucleosome and chromatin structure (Part 1)

6. Figure 2.2 Nucleosome and chromatin structure (Part 2)

7. Figure 2.2 Nucleosome and chromatin structure (Part 3)

8. Figure 2.2 Nucleosome and chromatin structure (Part 4)

9. Figure 2.3 Histone methylations on histone H3

10. Figure 2.4 Nucleotide sequence of the human -globin gene (Part 1)

11. Figure 2.4 Nucleotide sequence of the human -globin gene (Part 2)

12. Figure 2.5 Steps in the production of -globin and hemoglobin

13. Figure 2.6 The bridge between enhancer and promoter can be made by transcription factors

14. Figure 2.7 The role of the Mediator complex in forming the transcription pre-initiation complex -Mediator complex links the enhancer and promoter to form the initiation complex

15. Figure 2.7 The role of the Mediator complex in forming the transcription pre-initiation complex (Part 1)

16. Figure 2.7 The role of the Mediator complex in forming the transcription pre-initiation complex (Part 2)

17. Figure 2.8 The genetic elements regulating tissue-specific transcription can be identified by fusing reporter genes to suspected enhancer regions of the genes expressed in particular cell types

18. Figure 2.8 The genetic elements regulating tissue-specific transcription can be identified by fusing reporter genes to suspected enhancer regions of the genes expressed in particular cell types (Part 1)

19. Figure 2.8 The genetic elements regulating tissue-specific transcription can be identified by fusing reporter genes to suspected enhancer regions of the genes expressed in particular cell types (Part 2)

20. Figure 2.9 Enhancer region modularity -Enhancer region may have multiple modules for differential gene expression -Each module may need combinatorial association with specific transcription factors for the gene expression

21. Figure 2.9 Enhancer region modularity (Part 1)

22. Figure 2.9 Enhancer region modularity (Part 2)

23. Figure 2.9 Enhancer region modularity (Part 3)

24. Figure 2.10 Modular transcriptional regulatory regions using Pax6 as an activator

25. Table 2.1 Some major transcription factor families and subfamilies Pioneer transcription factor: open up the repressed chromatin and maintain activation status

26. Figure 2.11 Three-dimensional model of the homodimeric transcription factor MITF (one protein shown in red, the other in blue) binding to a promoter element in DNA (white)

27. Figure 2.12 Pancreatic lineage and transcription factors

28. Figure 2.12 Pancreatic lineage and transcription factors (Part 1)

29. Figure 2.12 Pancreatic lineage and transcription factors (Part 2)

30. Figure 2.13 A silencer represses gene transcription

31. Figure 2.14 Chromatin immunoprecipitation-sequencing (ChIPSeq)

32. Figure 2.14 Chromatin immunoprecipitation-sequencing (ChIPSeq) (Part 1)

33. Figure 2.14 Chromatin immunoprecipitation-sequencing (ChIPSeq) (Part 2)

34. Figure 2.15 Chromatin regulation in HCPs and LCPs

35. Figure 2.15 Chromatin regulation in HCPs and LCPs (Part 1) HCPs are usually found in developmental control genes such as transcription factors HCPs are usually not methylated The default status of HCPs are Open chromatin and the elongation is critical step for gene expression

36. Figure 2.15 Chromatin regulation in HCPs and LCPs (Part 2) LCPs are usually found in developmental control genes such as transcription factors LCPs are usually methylated The default status of LCPs is inactive form. A specific transcription factor can initiate the gene expression.

37. Figure 2.21 Model for the regulation of RNA elongation by the Mediator protein Med26

38. Figure 2.16 Methylation of globin genes in human embryonic blood cells

39. Figure 2.16 Methylation of globin genes in human embryonic blood cells (Part 1)

40. Figure 2.16 Methylation of globin genes in human embryonic blood cells (Part 2)

41. Figure 2.17 DNA methylation can block transcription by preventing transcription factors from binding to the enhancer region

42. Figure 2.18 Modifying nucleosomes through methylated DNA

43. Figure 2.18 Modifying nucleosomes through methylated DNA (Part 1)

44. Figure 2.18 Modifying nucleosomes through methylated DNA (Part 2)

45. Figure 2.19 Two DNA methyltransferases are critically important in modifying DNA

46. Figure 2.20 Regulation of the imprinted Igf2 gene in the mouse

47. Figure 2.23 Inheritance patterns for Prader-Willi and Angelman syndromes

48. Figure 15.36 Differential DNA methylation patterns in aging twins

49. Figure 15.37 Methylation of the estrogen receptor gene occurs as a function of normal aging

50. Figure 17.19 Cancer can arise (A) if tumor-suppressor genes are inappropriately turned off by DNA methylation or (B) if oncogenes are inappropriately demethylated