BIOLOGY. Chapter 16 GenesExpression

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1 BIOLOGY Chapter 16 GenesExpression

2 CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson 18 Gene Expression 2014 Pearson Education, Inc.

3 Figure 16.1 Differential Gene Expression results in you Genetic content is the same, Not all genes are expressed in every cell differential gene expression patterns

4 Fig / 16.1 Control of Gene Differential Gene Expression

5 Figure 18.2 Precursor Remember Negative Feedback Regulation? Feedback inhibition Enzyme 1 trpe Enzyme 2 trpd trpc Regulation of gene expression Enzyme 3 trpb trpa Tryptophan (a) Regulation of enzyme activity (b) Regulation of enzyme production

6 Figure 18.3 / 16.3 Prokaryotic control of gene expression Promoter mrna 5 trpr Regulatory gene 3 RNA polymerase Promoter Operator Start codon mrna 5 trp operon Genes of operon trpe trpd trpc trpb trpa Stop codon Protein Inactive repressor (a) Tryptophan absent, repressor inactive, operon on E D C B A Polypeptide subunits that make up enzymes for tryptophan synthesis mrna 5 Protein trpr 3 Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off trpe Active repressor No RNA made Bacterial Gene Expression Control: Operon: cluster of genes & includes: Promoter region (TATA/operator) Operator (on/off switch) Genes being expressed Two types of Operons Repressible always ON Repressor inactive Inducible always OFF Repressor active Corepressor Regulatory Gene upstream

7 Figure 18.3a Tryptophan (Trp) operon Repressible Operon Always ON Repressor inactive transcription of genes enzyme for tryptophan synthesis trp operon Promoter Regulatory gene Promoter Genes of operon trpr trpe trpd trpc trpb trpa mrna 5 3 RNA polymerase Operator Start codon mrna 5 Stop codon Protein Inactive repressor (a) Tryptophan absent, repressor inactive, operon on E D C B A Polypeptide subunits that make up enzymes for tryptophan synthesis

8 Figure 18.3b Trp operon Repressible Operon Corepressor + Active repressor turned OFF (repressed) Too much tryptophan trp acts as a corepressor, activating repressor mrna 5 trpr 3 trpe No RNA made Protein Tryptophan (corepressor) Active repressor (b) Tryptophan present, repressor active, operon off

9 Figure 18.4 / 16.4 & 16.5 Regulatory gene l a Ic Promoter Operator Lactose operon Inducible Operon Always OFF IacZ mrna 5 3 RNA polymerase No RNA made Protein Active repressor (a) Lactose absent, repressor active, operon off l a Ic lac operon lacz lacy laca mrna RNA polymerase Start codon Stop codon mrna 5 Protein β-galactosidase Permease Transacetylase Allolactose (inducer) Inactive repressor (b) Lactose present, repressor inactive, operon on

10 Figure 18.4a lac operon: Inducible Operon Active repressor genes turned OFF No Lactose no gene expression, no enzymes to breakdown lactose Regulatory gene Promoter Operator lac I IacZ mrna 5 3 RNA polymerase No RNA made Protein Active repressor (a) Lactose absent, repressor active, operon off

11 Figure 18.4b lac operon: Inducible Operon INactive repressor genes turned ON Lactose (Inducer) present repressor inactive gene expression (induced) lac operon lac I lacz lacy laca mrna 3 RNA polymerase Start codon Stop codon 5 mrna 5 Protein β-galactosidase Permease Transacetylase Inactive repressor Allolactose (inducer) (b) Lactose present, repressor inactive, operon on

12 Figure 18.5 / 16.4 Positive control of lac operon by Catabolite Activator Protein (CAP) lac I CAP-binding site camp Promoter Active CAP Operator RNA polymerase binds and transcribes lacz Inactive CAP Allolactose Inactive lac repressor (a) Lactose present, glucose scarce (camp level high): abundant lac mrna synthesized Promoter lac I lacz CAP-binding site Inactive CAP Operator RNA polymerase less likely to bind Inactive lac repressor (b) Lactose present, glucose present (camp level low): little lac mrna synthesized

13 Figure 18.5a / 16.4 lac I Promoter Positive control of lac operon by Catabolite Activator Protein (CAP) Operator lacz CAP-binding site camp Active CAP RNA polymerase binds and transcribes Inactive CAP Allolactose Inactive lac repressor (a) Lactose present, glucose scarce (camp level high): abundant lac mrna synthesized CAP helps regulate operons (increases when glucose is low)

14 Figure 18.5b Positive control of the lac operon by CAP Positive control of lac operon by Catabolite Activator Protein (CAP) lac I Promoter lacz CAP-binding site Inactive CAP Operator RNA polymerase less likely to bind Inactive lac repressor (b) Lactose present, glucose present (camp level low): little lac mrna synthesized CAP helps regulate operons (when glucose is high, CAP detaches) When glucose levels increase, CAP detaches, normal expression

15 Fig Promoter Lac operon inducible operon Operator laci CAP-binding site camp Active CAP lacz RNA polymerase binds and transcribes Inactive CAP Allolactose Inactive lac repressor (a) Lactose present, glucose scarce (camp level high): abundant lac mrna synthesized laci CAP-binding site Inactive CAP Promoter Operator lacz RNA polymerase less likely to bind Inactive lac repressor (b) Lactose present, glucose present (camp level low): little lac mrna synthesized

16 Figure 16.5 Transcription of the lac operon regulated Expression only occurs when: glucose is limited lactose is present (alternative fuel source)

17 Figure 18.6 Control of gene expression Signal Chromatin Chromatin modification: unpacking Gene available for transcription Transcription Cap RNA NUCLEUS CYTOPLASM Degradation of mrna Exon Intron Primary transcript RNA processing Tail mrna in nucleus Transport to cytoplasm mrna in cytoplasm Translation Polypeptide Protein processing Degradation of protein Active protein Transport to cellular destination Cellular function (such as enzymatic activity or structural support)

18 Figure 18.6 Control of gene expression Signal Chromatin Chromatin modification: unpacking Gene available for transcription 1) Chromatin modification (epigenetics) 2) Pre-transcription (transcriptional factor & activators) 3) Post-transcription (RNA Processing) 4) Pre-translation & mrna degradation 5) Post-translation (protein processing) 6) Protein degradation Cap RNA NUCLEUS CYTOPLASM Degradation of mrna Exon Intron Transcription Primary transcript RNA processing Tail mrna in nucleus Transport to cytoplasm mrna in cytoplasm Translation Polypeptide Protein processing Degradation of protein Active protein Transport to cellular destination Cellular function (such as enzymatic activity or structural support)

19 Figure 18.6a Control of gene expression Signal Chromatin 1) Chromatin modification Histone acetylation methylation Epigenetic inheritance Gene available for transcription Cap RNA Chromatin modification: unpacking Exon Intron Transcription Primary transcript RNA processing Tail mrna in nucleus NUCLEUS Transport to cytoplasm CYTOPLASM

20 Figure 18.7 / 16.7 Histone Acetylation favors transcription Histone tails Amino acids available for chemical modification double helix Nucleosome (end view) (a) Histone tails protrude outward from a nucleosome Acetyl groups Unacetylated histones (side view) Acetylated histones (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription

21 Figure 16.8 Epigenetics

22 Epigenetic & Methylation Chromosome 15 Angelman Syndrome Maternal expressed Paternal silenced Prader-Willi Syndrome Paternal expressed Maternal silenced (deletion)

23 Figure 18.6a Control of gene expression Signal Chromatin 1) Chromatin modification 2) Pre-transcription Transcription initiation Chromatin modification: unpacking Gene available for transcription Transcription Cap RNA Exon Intron Primary transcript RNA processing Tail mrna in nucleus NUCLEUS Transport to cytoplasm CYTOPLASM

24 Figure 18.8 Control of gene expression 2) Regulation of Transcription Initiation (pre-transcription) Transcriptional factors bind to enhancers Transcriptional factors bind Enhancer (group of distal control elements) Proximal control elements Transcription start site Exon Intron Exon Intron Poly-A signal sequence Exon Transcription termination region Upstream Primary RNA transcript (pre-mrna) Promoter 5 Exon Intron Exon Transcription Intron Downstream Poly-A signal Exon Cleaved 3 end of primary transcript Intron RNA RNA processing Coding segment mrna G P P P 5 Cap 5 UTR Start codon Stop codon AAA AAA 3 UTR Poly-A tail 3

25 Figure / 16.9 Activators Promoter Enhancer Distal control element TATA box Gene Control of Gene Expression 2) Regulation of Transcription Initiation (pre-transcription) Transcriptional factors bind to enhancers Activators stimulates transcription bending protein General transcription factors Group of mediator proteins RNA polymerase II RNA polymerase II Transcription initiation complex RNA synthesis

26 Figure Cell specific transcription in both cells contains the albumin gene and the crystallin gene: Control elements Enhancer for albumin gene Promoter Enhancer for crystallin gene Promoter Albumin gene Crystallin gene LIVER CELL NUCLEUS Available activators LENS CELL NUCLEUS Available activators Albumin gene expressed Albumin gene not expressed (a) Liver cell Crystallin gene not expressed (b) Lens cell Crystallin gene expressed

27 Figure 18.6a Control of gene expression Signal Chromatin 1) Chromatin modification 2) Pre-transcription Transcription initiation 3) Post-transcription RNA Processing Chromatin modification: unpacking Gene available for transcription Transcription Cap RNA Exon Intron Primary transcript RNA processing Tail mrna in nucleus NUCLEUS Transport to cytoplasm CYTOPLASM

28 Fig Control of Gene Expression 3) Post-transcription RNA processing Enhancer (distal control elements) Upstream Proximal control elements Promoter Exon Intron Exon Poly-A signal sequence Termination region Intron Exon Transcription Downstream Primary RNA transcript 5 Exon Intron Exon Intron Exon RNA processing Cleaved 3 end of primary transcript Intron RNA Poly-A signal Coding segment mrna 5 Cap 5 UTR Start codon Stop codon 3 UTR Poly-A tail 3

29 Post-transcription alternative splicing & mrna degradation Fig / Exons Troponin T gene Primary RNA transcript RNA splicing mrna or

30 Figure There are five basic modes of alternative splicing.

31 Figure 18.6b Control of gene expression CYTOPLASM mrna in cytoplasm Degradation of mrna Translation 1) Chromatin modification 2) Pre-transcription Transcription initiation 3) Post-transcription RNA Processing 4) Pre-translation Degradation of protein Translation initiation & mrna degradation Polypeptide Protein processing Active protein Transport to cellular destination Cellular function (such as enzymatic activity or structural support)

32 Fig Hairpin mirna Hydrogen bond Dicer 5 3 (a) Primary mirna transcript mirna mirnaprotein complex Pre-translation & mrna degradation RNAi RNA interference caused by: mirna blocks translation sirna blocks transcription Both: degrade mrna & chromatin modification mrna degraded Translation blocked (b) Generation and function of mirnas

33 Figure mirna mirnaprotein complex 1 The mirna binds to a target mrna. OR mrna degraded Translation blocked 2 If bases are completely complementary, mrna is degraded. If match is less than complete, translation is blocked.

34 Figure 18.6b Control of gene expression CYTOPLASM mrna in cytoplasm 1) Chromatin modification 2) Pre-transcription 3) Post-transcription 4) Pre-translation 5) Protein Processing Degradation of mrna Degradation of protein Translation Polypeptide Protein processing Active protein Transport to cellular destination Cellular function (such as enzymatic activity or structural support)

35 Figure 18.6b Control of gene expression CYTOPLASM mrna in cytoplasm 1) Chromatin modification 2) Pre-transcription 3) Post-transcription 4) Pre-translation 5) Protein Processing 6) Protein Degradation Degradation of mrna Degradation of protein Translation Polypeptide Protein processing Active protein Transport to cellular destination Cellular function (such as enzymatic activity or structural support)

36 Fig / Post-translation protein degradation Ubiquitin Proteasome Proteasome and ubiquitin to be recycled Protein to be degraded Ubiquitinated protein Protein entering a proteasome Protein fragments (peptides)

37 Fig Nucleus Master regulatory gene myod Other muscle-specific genes Embryonic precursor cell OFF OFF mrna OFF Myoblast (determined) MyoD protein (transcription factor) mrna mrna mrna mrna Part of a muscle fiber (fully differentiated cell) MyoD Another transcription factor Myosin, other muscle proteins, and cell cycle blocking proteins

38 Fig Nucleus Master regulatory gene myod Determination & Differentiation of cells Other muscle-specific genes Embryonic precursor cell OFF OFF mrna OFF Myoblast (determined) MyoD protein (transcription factor) mrna mrna mrna mrna Part of a muscle fiber (fully differentiated cell) MyoD Another transcription factor Myosin, other muscle proteins, and cell cycle blocking proteins

39 Fig Growth factor 3 G protein GTP Ras GTP Ras MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own 2 Receptor 4 Protein kinases (phosphorylation cascade) 5 Transcription factor (activator) NUCLEUS Gene expression Protein that stimulates the cell cycle (a) Cell cycle stimulating pathway 2 Protein kinases MUTATION UV light 3 Active form of p53 Defective or missing transcription factor, such as p53, cannot activate transcription 1 damage in genome Protein that inhibits the cell cycle (b) Cell cycle inhibiting pathway EFFECTS OF MUTATIONS Protein overexpressed Protein absent Cell cycle overstimulated Increased cell division Cell cycle not inhibited (c) Effects of mutations

40 Fig c EFFECTS OF MUTATIONS Protein overexpressed Protein absent Cell cycle overstimulated Increased cell division Cell cycle not inhibited (c) Effects of mutations

41 Fig Colon EFFECTS OF MUTATIONS Colon wall 1 Loss of tumorsuppressor gene APC (or other) 2 Activation of ras oncogene 4 Loss of tumor-suppressor gene p53 Normal colon epithelial cells Small benign growth (polyp) 3 Loss of tumor-suppressor gene DCC Larger benign growth (adenoma) 5 Additional mutations Malignant tumor (carcinoma)

42 Fig

43 Fig. 18-UN1 Operon Promoter Operator RNA polymerase A Genes B C A B C Polypeptides

44 Fig. 18-UN2 Promoter Genes expressed Operator Genes Inactive repressor: no corepressor present Genes not expressed Corepressor Active repressor: corepressor bound

45 Fig. 18-UN3 Genes not expressed Promoter Genes expressed Operator Genes Active repressor: no inducer present Inactive repressor: inducer bound

46 Figure 18.UN09 Chromatin modification Genes in highly compacted chromatin are generally not transcribed. Histone acetylation seems to loosen chromatin structure, enhancing transcription. methylation generally reduces transcripton. Transcription Regulation of transcription initiation: control elements in enhancers bind specific transcription factors. Bending of the enables activators to contact proteins at the promoter, initiating transcription. Coordinate regulation: CHROMATIN MODIFICATION Enhancer for liver-specific genes Enhancer for lens-specific genes mrna DEGRADATION TRANSCRIPTION RNA PROCESSING TRANSLATION PROTEIN PROCESSING AND DEGRADATION mrna degradation Each mrna has a characteristic life span, determined in part by sequences in the 5 and 3 UTRs. RNA processing Alternative RNA splicing: Primary RNA transcript mrna OR Translation Initiation of translation can be controlled via regulation of initiation factors. Protein processing and degradation Protein processing and degradation are subject to regulation.

47 Figure 18.UN09b Chromatin modification Genes in highly compacted chromatin are generally not transcribed. Histone acetylation seems to loosen chromatin structure, enhancing transcription. methylation generally reduces transcription. mrna degradation Each mrna has a characteristic life span, determined in part by sequences in the 5 and 3 UTRs. RNA processing Alternative RNA splicing: Primary RNA transcript mrna OR Translation Initiation of translation can be controlled via regulation of initiation factors. Protein processing and degradation Protein processing and degradation are subject to regulation.

48 Fig. 18-UN4 Chromatin modification Genes in highly compacted chromatin are generally not transcribed. Histone acetylation seems to loosen chromatin structure, enhancing transcription. Transcription Regulation of transcription initiation: control elements bind specific transcription factors. methylation generally reduces transcription. Bending of the enables activators to contact proteins at the promoter, initiating transcription. Coordinate regulation: Enhancer for liver-specific genes Enhancer for lens-specific genes Chromatin modification mrna degradation Transcription RNA processing Translation Primary RNA transcript mrna RNA processing Alternative RNA splicing: or Protein processing and degradation mrna degradation Each mrna has a characteristic life span, determined in part by sequences in the 5 and 3 UTRs. Translation Initiation of translation can be controlled via regulation of initiation factors. Protein processing and degradation Protein processing and degradation by proteasomes are subject to regulation.

49 Fig. 18-UN5 Chromatin modification Transcription Chromatin modification Small RNAs can promote the formation of heterochromatin in certain regions, blocking transcription. RNA processing Translation mirna or sirna can block the translation of specific mrnas. mrna degradation Translation Protein processing and degradation mrna degradation mirna or sirna can target specific mrnas for destruction.