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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 18 Regulation of Gene Expression.

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Presentation on theme: "Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 18 Regulation of Gene Expression."— Presentation transcript:

1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 18 Regulation of Gene Expression

2 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Prokaryotes and eukaryotes alter gene expression in response to their changing environment Eukaryotes, gene expression regulates development RNA many roles in regulating gene expression in eukaryotes © 2011 Pearson Education, Inc.

3 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Regulation of gene expression in bacteria Natural selection production of only products needed by that cell Gene expression in bacteria = operon model © 2011 Pearson Education, Inc.

4 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Precursor Feedback inhibition Enzyme 1 Enzyme 2 Enzyme 3 Tryptophan (a) (b) Regulation of enzyme activity Regulation of enzyme production Regulation of gene expression trpE gene trpD gene trpC gene trpB gene trpA gene Figure 18.2

5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Promoter DNA Regulatory gene mRNA trpR 5 3 Protein Inactive repressor RNA polymerase Promoter trp operon Genes of operon Operator mRNA 5 Start codonStop codon trpEtrpDtrpC trpB trpA EDCBA Polypeptide subunits that make up enzymes for tryptophan synthesis (a) Tryptophan absent, repressor inactive, operon on (b) Tryptophan present, repressor active, operon off DNA mRNA Protein Tryptophan (corepressor) Active repressor No RNA made Figure 18.3

6 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.3a Promoter DNA Regulatory gene mRNA trpR 5 3 Protein Inactive repressor RNA polymerase Promoter trp operon Genes of operon Operator mRNA 5 Start codonStop codon trpEtrpDtrpC trpB trpA EDCBA Polypeptide subunits that make up enzymes for tryptophan synthesis (a) Tryptophan absent, repressor inactive, operon on

7 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.3b-1 (b) Tryptophan present, repressor active, operon off DNA mRNA Protein Tryptophan (corepressor) Active repressor

8 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.3b-2 (b) Tryptophan present, repressor active, operon off DNA mRNA Protein Tryptophan (corepressor) Active repressor No RNA made

9 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Repressible and Inducible Operons: 2 Types of Negative Gene Regulation A repressible operon is one that is usually on; binding of a repressor to the operator shuts off transcription The trp operon is a repressible operon An inducible operon is one that is usually off; a molecule called an inducer inactivates the repressor and turns on transcription © 2011 Pearson Education, Inc.

10 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose © 2011 Pearson Education, Inc.

11 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (a) Lactose absent, repressor active, operon off (b) Lactose present, repressor inactive, operon on Regulatory gene Promoter Operator DNA lacZlac I DNA mRNA 5 3 No RNA made RNA polymerase Active repressor Protein lac operon lacZlacYlacADNA mRNA 5 3 Protein mRNA 5 Inactive repressor RNA polymerase Allolactose (inducer) -Galactosidase PermeaseTransacetylase Figure 18.4

12 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.4a (a) Lactose absent, repressor active, operon off Regulatory gene Promoter Operator DNA lacZ lac I DNA mRNA 5 3 No RNA made RNA polymerase Active repressor Protein

13 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.4b (b) Lactose present, repressor inactive, operon on lac I lac operon lacZlacYlacADNA mRNA 5 3 Protein mRNA 5 Inactive repressor RNA polymerase Allolactose (inducer) -Galactosidase PermeaseTransacetylase

14 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Eukaryotic gene expression regulated at many stages All organisms must regulate which genes are expressed at any given time © 2011 Pearson Education, Inc.

15 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Differential Gene Expression Differences between cell types result from differential gene expression, the expression of different genes by cells with the same genome Abnormalities in gene expression can lead to diseases including cancer © 2011 Pearson Education, Inc.

16 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.6a Signal NUCLEUS Chromatin Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation DNA Gene Gene available for transcription RNA Exon Primary transcript Transcription Intron RNA processing Cap Tail mRNA in nucleus Transport to cytoplasm CYTOPLASM

17 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.6b CYTOPLASM mRNA in cytoplasm Translation Degradation of mRNA Polypeptide Protein processing, such as cleavage and chemical modification Active protein Degradation of protein Transport to cellular destination Cellular function (such as enzymatic activity, structural support)

18 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.7 Amino acids available for chemical modification Histone tails DNA double helix Nucleosome (end view) (a) Histone tails protrude outward from a nucleosome Unacetylated histones Acetylated histones (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription

19 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA Methylation DNA methylation reduced transcription © 2011 Pearson Education, Inc.

20 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Organization of a Typical Eukaryotic Gene © 2011 Pearson Education, Inc.

21 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Enhancer (distal control elements) DNA Upstream Promoter Proximal control elements Transcription start site Exon IntronExon Intron Poly-A signal sequence Transcription termination region Downstream

22 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Enhancer (distal control elements) DNA Upstream Promoter Proximal control elements Transcription start site Exon IntronExon Intron Poly-A signal sequence Transcription termination region Downstream Poly-A signal Exon IntronExon Intron Transcription Cleaved 3 end of primary transcript 5 Primary RNA transcript (pre-mRNA)

23 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Enhancer (distal control elements) DNA Upstream Promoter Proximal control elements Transcription start site Exon IntronExon Intron Poly-A signal sequence Transcription termination region Downstream Poly-A signal Exon IntronExon Intron Transcription Cleaved 3 end of primary transcript 5 Primary RNA transcript (pre-mRNA) Intron RNA RNA processing mRNA Coding segment 5 Cap 5 UTR Start codon Stop codon 3 UTR 3 Poly-A tail P PPG AAA

24 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings RNA Processing © 2011 Pearson Education, Inc. Animation: RNA Processing

25 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Exons DNA Troponin T gene Primary RNA transcript RNA splicing or mRNA Figure 18.13

26 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Protein to be degraded Ubiquitin Ubiquitinated protein Proteasome Protein entering a proteasome Proteasome and ubiquitin to be recycled Protein fragments (peptides)

27 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Noncoding RNA Only a small fraction of DNA codes for proteins, and a very small fraction of the non-protein-coding DNA consists of genes for RNA such as rRNA and tRNA Significant amount noncoding RNAs (ncRNAs) © 2011 Pearson Education, Inc.

28 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effects on mRNAs by MicroRNAs and Small Interfering RNAs MicroRNAs (miRNAs) degrade mRNA or block its translation © 2011 Pearson Education, Inc.

29 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (a) Primary miRNA transcript Hairpin miRNA Hydrogen bond Dicer miRNA- protein complex mRNA degradedTranslation blocked (b) Generation and function of miRNAs 5 3 Figure 18.15

30 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings RNA interference (RNAi) Inhibition of gene expression © 2011 Pearson Education, Inc.

31 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Differential gene expression leads to different cell types Fertilized egg many different cell types Gene expression orchestrates development © 2011 Pearson Education, Inc.

32 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure (a) Fertilized eggs of a frog (b) Newly hatched tadpole 1 mm 2 mm

33 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.16a (a) Fertilized eggs of a frog 1 mm

34 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.16b (b) Newly hatched tadpole 2 mm

35 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell differentiation is the process by which cells become specialized in structure and function The physical processes that give an organism its shape constitute morphogenesis Differential gene expression results from genes being regulated differently in each cell type © 2011 Pearson Education, Inc.

36 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Induction signal molecules from embryonic cells cause transcriptional changes in nearby target cells differentiation of specialized cell types © 2011 Pearson Education, Inc. Animation: Cell Signaling

37 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.17b (b) Induction by nearby cells Early embryo (32 cells) NUCLEUS Signal transduction pathway Signal receptor Signaling molecule (inducer)

38 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pattern Formation Development of a spatial organization of tissues and organs © 2011 Pearson Education, Inc.

39 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Head Thorax Abdomen 0.5 mm BODY AXES Anterior Left Ventral Dorsal Right Posterior (a) Adult Egg developing within ovarian follicle Follicle cell Nucleus Nurse cell Egg Unfertilized egg Depleted nurse cells Egg shell Fertilization Laying of egg Fertilized egg Embryonic development Segmented embryo Body segments Hatching 0.1 mm Larval stage (b) Development from egg to larva Figure 18.19

40 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.19a Head Thorax Abdomen 0.5 mm BODY AXES Anterior Left Ventral Dorsal Right Posterior (a) Adult

41 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.19b Egg developing within ovarian follicle Follicle cell Nucleus Nurse cell Egg Unfertilized egg Depleted nurse cells Egg shell Fertilization Laying of egg Fertilized egg Embryonic development Segmented embryo Body segments Hatching 0.1 mm Larval stage (b) Development from egg to larva

42 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Analysis of Early Development: Scientific Inquiry Edward B. Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus (1995 Nobel Prize) decoding pattern formation in Drosophila Homeotic genes control pattern formation © 2011 Pearson Education, Inc.

43 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.20a Wild type Eye Antenna

44 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.20b Mutant Leg

45 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cancer results from genetic changes that affect cell cycle control The gene regulation systems that go wrong during cancer are the very same systems involved in embryonic development © 2011 Pearson Education, Inc.

46 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Types of Genes Associated with Cancer Cancer can be caused by mutations to genes that regulate cell growth and division Tumor viruses can cause cancer in animals including humans © 2011 Pearson Education, Inc.

47 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Oncogenes are cancer-causing genes Proto-oncogenes are the corresponding normal cellular genes that are responsible for normal cell growth and division © 2011 Pearson Education, Inc.

48 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls Gene amplification: multiple copies of the gene New promoter Normal growth- stimulating protein in excess Point mutation: within a control element within the gene Oncogene Normal growth- stimulating protein in excess Hyperactive or degradation- resistant protein

49 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tumor-Suppressor Genes Tumor-suppressor genes help prevent uncontrolled cell growth © 2011 Pearson Education, Inc.

50 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Growth factor Receptor G protein Protein kinases (phosphorylation cascade) NUCLEUS Transcription factor (activator) DNA Gene expression Protein that stimulates the cell cycle Hyperactive Ras protein (product of oncogene) issues signals on its own. (a) Cell cycle–stimulating pathway MUTATION Ras GTP P P P P P P (b) Cell cycle–inhibiting pathway Protein kinases UV light DNA damage in genome Active form of p53 DNA Protein that inhibits the cell cycle Defective or missing transcription factor, such as p53, cannot activate transcription. MUTATION EFFECTS OF MUTATIONS (c) Effects of mutations Protein overexpressed Cell cycle overstimulated Increased cell division Protein absent Cell cycle not inhibited 3

51 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Growth factor 1 Receptor G protein Protein kinases (phosphorylation cascade) NUCLEUS Transcription factor (activator) DNA Gene expression Protein that stimulates the cell cycle Hyperactive Ras protein (product of oncogene) issues signals on its own. (a) Cell cycle–stimulating pathway MUTATION Ras GTP P P P P P P 2345 Ras GTP Figure 18.24a

52 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.24b (b) Cell cycle–inhibiting pathway Protein kinases UV light DNA damage in genome Active form of p53 DNA Protein that inhibits the cell cycle Defective or missing transcription factor, such as p53, cannot activate transcription. MUTATION 213

53 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 18.24c EFFECTS OF MUTATIONS (c) Effects of mutations Protein overexpressed Cell cycle overstimulated Increased cell division Protein absent Cell cycle not inhibited

54 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Multistep Model of Cancer Development © 2011 Pearson Education, Inc.

55 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure Colon Normal colon epithelial cells Loss of tumor- suppressor gene APC (or other) Colon wall Small benign growth (polyp) Activation of ras oncogene Loss of tumor- suppressor gene DCC Loss of tumor- suppressor gene p53 Additional mutations Malignant tumor (carcinoma) Larger benign growth (adenoma)


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