1. Biochemistry Sixth Edition Chapter 31 The Control of Gene Expression Part II: Eukaryotes (nucleosomes & chromatin) Copyright © 2007 by W. H. Freeman and Company Berg Tymoczko Stryer

4. Chromatin structure: beads-on-a-string

7. Homologous histones Histones: half of the mass of chromosome

8. Nucleosome core particle Histone octamer (H3) 2 (H4) 2 + (H2A-H2B) x 2

9. Nucleosome core particle

10. DNA

11. DNA compaction by nucleosomes DNA Nuclesome Metaphase chromosome Ratio=7 Ratio=10 4

14. Gal4: DNA binding txn factor (activates genes for galatose metabolism) * Recognize 5’-CGG(N) 11 CGG-3’ * 4000 sites in yeast genome * Gal4 only binds to only 10 (most sites are blocked)

16. DNase hypersensitive sites * Regions with few nucleosomes or nuclesomes in altered conformational state * Cell type-specific and developmental-regulated Ex. Globin genes (expressed in blood cells) early embryo  DNase insensitive later development  highly sensitive brain cell  always DNase resistant

19. Coactivators catalyze acetylation of histone tail lysine

20. Histone acetyltransferase (HAT)

26. Acetyllysine-binding domain (present in txn regulators) Ex. bromodomain (110 amino acids, 4-helix bundle)

28. Modified histone tails  recruiting other components of txn machinery

29. Example #1 of bromodomain proteins

30. Example #2 of bromodomain proteins (chromatin-remodeling engines)  Helicase (ATP hydrolysis)

31. Remodeling of chromatin structure!

34. Biochemistry Sixth Edition Chapter 31 The Control of Gene Expression Part III: Post-transcriptional regulation Copyright © 2007 by W. H. Freeman and Company Berg Tymoczko Stryer

35. Post-transcriptional regulation: 1.Another level of regulation 2.Different between prok. & euk. 3.Involves special structure of mRNA

36. Post-transcriptional regulation: 1.Secondary structure in translation 2.Alternative splicing 3.RNA interference (RNAi)

37. Attenuation: prokaryotic transcriptional regulation tryptophan operon leader region of trp mRNA Tryptophan level High: first 130 nt of mRNA  no protein Low: 7000 nt trp mRNA  Termination site: attenuator

38. Attenuator region can form two distinct stem-loop structure Also: txn and translation are coupled in prok.

39. High tryptophan (& trp-tRNA)

40. low tryptophan (& trp-tRNA) Sensing supply of nutrient for protein synthesis

41. Other operons for amino acid biosynthesis in E. coli threonine & isoleucine phenylalanine histidine

42. Euk. translational regulation: iron metabolism Iron: required for synthesis of many proteins (ex. hemoglobin) Too much iron: free radical reactions  cell damages Transferrin: carries iron in the serum Transferrin receptor: membrane protein, transport transferrin into cells Ferritin: iron-storage protein

43. Structure of ferritin Iron is low: transferrin receptor increases & ferritin decreases but mRNAs stay the same

44. Iron-response element (IRE) in ferritin mRNA  Blocks translation initiation IRE-binding protein (IRP) (iron-sensing protein)

45. In IRP, 4Fe-4S cluster and RNA binding sites overlap for ferritin  translation  No translation

46. Iron-response element (IRE) in transferrin-receptor mRNA  mRNA stability

47. In IRP, 4Fe-4S cluster and RNA binding sites overlap for transferrin receptor  mRNA degradation  translation