1) Gene expression in prokaryotes and eukaryotes is regulated in response to environmental changes through various mechanisms at the transcriptional and post-transcriptional levels. 2) In bacteria, operons control transcription of clusters of genes in response to stimuli like small molecules. Repressible and inducible operons use allosteric effectors to turn transcription on or off. 3) In eukaryotes, gene expression is controlled through chromatin modifications, transcription factors, RNA processing, and noncoding RNAs that regulate mRNA translation and chromatin structure. Cancer results from genetic changes affecting cell cycle control genes.

1. Control of Gene Expression AP Chap 18

4. Fig. 18-2 Regulation of gene expression trpE gene trpD gene trpC gene trpB gene trpA gene (b) Regulation of enzyme production (a) Regulation of enzyme activity Enzyme 1 Enzyme 2 Enzyme 3 Tryptophan Precursor Feedback inhibition

8. Fig. 18-4a (a) Lactose absent, repressor active, operon off DNA Protein Active repressor RNA polymerase Regulatory gene Promoter Operator mRNA 5  3  No RNA made lac I lacZ

9. Lactose present, repressor inactive, operon ON Fig. 18-4b (b) Lactose present, repressor inactive, operon on mRNA Protein DNA mRNA 5  Inactive repressor Allolactose (inducer) 5  3  RNA polymerase Permease Transacetylase lac operon  -Galactosidase lacY lacZ lacA lac I

11. Tryptophan absent, repressor inactive, operon ON Fig. 18-3a Polypeptide subunits that make up enzymes for tryptophan synthesis (a) Tryptophan absent, repressor inactive, operon on DNA mRNA 5  Protein Inactive repressor RNA polymerase Regulatory gene Promoter Promoter trp operon Genes of operon Operator Stop codon Start codon mRNA trpA 5  3  trpR trpE trpD trpC trpB A B C D E

12. Tryptophan present, repressor active, operon OFF Fig. 18-3b-1 (b) Tryptophan present, repressor active, operon off Tryptophan (corepressor) No RNA made Active repressor mRNA Protein DNA

13. INDUCIBLE REPRESSABLE OFF ON turned on by turned off by inducer corepressor used in catabolic used in anabolic pathways pathways Both use allosteric effectors and are NEGATIVE CONTROL.

15. Fig. 18-5 (b) Lactose present, glucose present (cAMP level low): little lac mRNA synthesized cAMP DNA Inactive lac repressor Allolactose Inactive CAP lac I CAP-binding site Promoter Active CAP Operator lacZ RNA polymerase binds and transcribes Inactive lac repressor lacZ Operator Promoter DNA CAP-binding site lac I RNA polymerase less likely to bind Inactive CAP (a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized

17. Control of Gene Expression in Eukaryotes

20. Eukaryotic gene expression can be regulated at any stage < A>

21. Fig. 18-6 DNA Signal Gene NUCLEUS Chromatin modification Chromatin Gene available for transcription Exon Intron Tail RNA Cap RNA processing Primary transcript mRNA in nucleus Transport to cytoplasm mRNA in cytoplasm Translation CYTOPLASM Degradation of mRNA Protein processing Polypeptide Active protein Cellular function Transport to cellular destination Degradation of protein Transcription

22. Fig. 18-6a DNA Signal Gene NUCLEUS Chromatin modification Chromatin Gene available for transcription Exon Intron Tail RNA Cap RNA processing Primary transcript mRNA in nucleus Transport to cytoplasm CYTOPLASM Transcription

23. Fig. 18-6b mRNA in cytoplasm Translation CYTOPLASM Degradation of mRNA Protein processing Polypeptide Active protein Cellular function Transport to cellular destination Degradation of protein

29. Fig. 18-9-1 Enhancer TATA box Promoter Activators DNA Gene Distal control element

30. Fig. 18-9-2 Enhancer TATA box Promoter Activators DNA Gene Distal control element Group of mediator proteins DNA-bending protein General transcription factors

31. Fig. 18-9-3 Enhancer TATA box Promoter Activators DNA Gene Distal control element Group of mediator proteins DNA-bending protein General transcription factors RNA polymerase II RNA polymerase II Transcription initiation complex RNA synthesis

33. Fig. 18-UN7

34. Fig. 18-10 Control elements Enhancer Available activators Albumin gene (b) Lens cell Crystallin gene expressed Available activators LENS CELL NUCLEUS LIVER CELL NUCLEUS Crystallin gene Promoter (a) Liver cell Crystallin gene not expressed Albumin gene expressed Albumin gene not expressed

36. Fig. 18-11 or RNA splicing mRNA Primary RNA transcript Troponin T gene Exons DNA

38. Fig. 18-12 Proteasome and ubiquitin to be recycled Proteasome Protein fragments (peptides) Protein entering a proteasome Ubiquitinated protein Protein to be degraded Ubiquitin

42. Fig. 18-13 miRNA- protein complex (a) Primary miRNA transcript Translation blocked Hydrogen bond (b) Generation and function of miRNAs Hairpin miRNA miRNA Dicer 3  mRNA degraded 5 

47. Fig. 18-21c (c) Effects of mutations EFFECTS OF MUTATIONS Cell cycle not inhibited Protein absent Increased cell division Protein overexpressed Cell cycle overstimulated

50. Fig. 18-20 Normal growth- stimulating protein in excess New promoter DNA Proto-oncogene Gene amplification: Translocation or transposition: Normal growth-stimulating protein in excess Normal growth- stimulating protein in excess Hyperactive or degradation- resistant protein Point mutation: Oncogene Oncogene within a control element within the gene

53. p53 gene and DNA repair Fig. 18-21b MUTATION Protein kinases DNA DNA damage in genome Defective or missing transcription factor, such as p53, cannot activate transcription Protein that inhibits the cell cycle Active form of p53 UV light (b) Cell cycle–inhibiting pathway 2 3 1

54. P53 and suicide genes