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Control of Gene Expression AP Chap 18
Overview: Conducting the Genetic Orchestra ,[object Object]
Bacteria often respond to environmental change by regulating transcription ,[object Object],[object Object],[object Object]
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
OPERONS ,[object Object],[object Object]
[object Object],Makes a repressor which binds to operator and stops/starts transcription RNA polymerase binds here
Induction System ,[object Object],[object Object],[object Object],[object Object],[object Object]
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
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
Repressible System ,[object Object],[object Object],[object Object]
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
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
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.
Positive Gene Regulation ,[object Object],[object Object],[object Object]
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
[object Object],[object Object]
Control of Gene Expression in Eukaryotes
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
Eukaryotic gene expression can be regulated at any stage < A>
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
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
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
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],There may be more to inheritance than genes alone. New clues reveal that a second epigenetic chemical code sits on top of our regular DNA and controls how our genes are expresse.
2) Transcription Level ,[object Object]
Transcription Factors: General ,[object Object],[object Object]
Specific Transcription Factors ,[object Object],[object Object],[object Object]
Fig. 18-9-1 Enhancer TATA box Promoter Activators DNA Gene Distal control element
Fig. 18-9-2 Enhancer TATA box Promoter Activators DNA Gene Distal control element Group of mediator proteins DNA-bending protein General transcription factors
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
 
Fig. 18-UN7
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
3.  Post-transcriptional Control ,[object Object],[object Object]
Fig. 18-11 or RNA splicing mRNA Primary RNA transcript Troponin T gene Exons DNA
[object Object],[object Object]
Fig. 18-12 Proteasome and ubiquitin to be recycled Proteasome Protein fragments (peptides) Protein entering a proteasome Ubiquitinated protein Protein to be degraded Ubiquitin
Noncoding RNAs play multiple roles in controlling gene expression ,[object Object],[object Object],[object Object]
Effects on mRNAs by MicroRNA’s ,[object Object],[object Object]
Hairpins? ,[object Object],[object Object]
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 
[object Object]
Small Interfering RNA’s ,[object Object],[object Object],[object Object]
CANCER AND GENE EXPRESSION Cancer results from genetic changes that affect cell cycle control ,[object Object],[object Object]
 
Fig. 18-21c (c) Effects of mutations EFFECTS OF MUTATIONS Cell cycle not inhibited Protein absent Increased cell division Protein overexpressed Cell cycle overstimulated
Oncogenes and Proto-Oncogenes ,[object Object],[object Object]
Conversion of a proto-oncogene to an oncogene can lead to abnormal stimulation of the cell cycle ,[object Object],[object Object],[object Object]
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
Tumor-Suppressor Genes ,[object Object],[object Object],[object Object],[object Object],[object Object]
How do cancer genes work? ,[object Object],[object Object],[object Object]
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
P53  and suicide genes
Multistep Model of Cancer Development ,[object Object],[object Object],[object Object],Breat cancer gene
Inherited Predisposition and Other Factors Contributing to Cancer ,[object Object],[object Object],[object Object]
[object Object],[object Object]

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Ap Chap 18 Pp

  • 1. Control of Gene Expression AP Chap 18
  • 2.
  • 3.
  • 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
  • 5.
  • 6.
  • 7.
  • 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
  • 10.
  • 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.
  • 14.
  • 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
  • 16.
  • 17. Control of Gene Expression in Eukaryotes
  • 18.
  • 19.
  • 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
  • 24.
  • 25.
  • 26.
  • 27.
  • 28.
  • 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
  • 32.  
  • 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
  • 35.
  • 36. Fig. 18-11 or RNA splicing mRNA Primary RNA transcript Troponin T gene Exons DNA
  • 37.
  • 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
  • 39.
  • 40.
  • 41.
  • 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 
  • 43.
  • 44.
  • 45.
  • 46.  
  • 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
  • 48.
  • 49.
  • 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
  • 51.
  • 52.
  • 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
  • 55.
  • 56.
  • 57.