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Regulation of Gene Expression 11. Chapter 11 Regulation of Gene Expression Key Concepts 11.1 Several Strategies Are Used to Regulate Gene Expression 11.2.

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Presentation on theme: "Regulation of Gene Expression 11. Chapter 11 Regulation of Gene Expression Key Concepts 11.1 Several Strategies Are Used to Regulate Gene Expression 11.2."— Presentation transcript:

1 Regulation of Gene Expression 11

2 Chapter 11 Regulation of Gene Expression Key Concepts 11.1 Several Strategies Are Used to Regulate Gene Expression 11.2 Many Prokaryotic Genes Are Regulated in Operons 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription

3 Chapter 11 Opening Question How does CREB regulate the expression of many genes?

4 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression Gene expression is tightly regulated. Gene expression may be modified to counteract environmental changes, or gene expression may change to alter function in the cell. Constitutive proteins are actively expressed all the time. Inducible genes are expressed only when their proteins are needed by the cell.

5 Figure 11.1 Potential Points for the Regulation of Gene Expression

6 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression Genes can be regulated at the level of transcription. Gene expression begins at the promoter where transcription is initiated. In selective gene transcription a decision is made about which genes to activate. Two types of regulatory proteinsalso called transcription factorscontrol whether a gene is active.

7 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression These proteins bind to specific DNA sequences near the promoter: Negative regulationa repressor protein prevents transcription Positive regulationan activator protein binds to stimulate transcription

8 Figure 11.2 Positive and Negative Regulation (Part 1)

9 Figure 11.2 Positive and Negative Regulation (Part 2)

10 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression Acellular viruses use gene regulation to take over host cells. A phage injects a host cell with nucleic acid that takes over synthesis. New viral particles (virions) appear rapidly and are soon released from the lysed cell. This lytic cycle is a typical viral reproductive cyclein a lysogenic phase, the viral genome is incorporated into the host genome and is replicated too.

11 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression A bacteriophage may contain DNA or RNA and may not have a lysogenic phase. The lytic cycle has two stages: Early stagepromoter in the viral genome binds host RNA polymerase and adjacent viral genes are transcribed Early genes shut down transcription of host genes, and stimulate viral replication and transcription of viral late genes. Host genes are shut down by a posttranscriptional mechanism. Viral nucleases digest the hosts chromosome for synthesis in new viral particles.

12 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression Late stageviral late genes are transcribed They encode the viral capsid proteins and enzymes to lyse the host cell and release new virions. The whole process from binding and infection to release of new particles takes about 30 minutes.

13 Figure 11.3 A Gene Regulation Strategy for Viral Reproduction

14 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression Human immunodeficiency virus (HIV) is a retrovirus with single-stranded RNA. HIV is enclosed in a membrane from the previous host cellit fuses with the new host cells membrane. After infection, RNA-directed DNA synthesis is catalyzed by reverse transcriptase. Two strands of DNA are synthesized and reside in the hosts chromosome as a provirus.

15 Figure 11.4 The Reproductive Cycle of HIV

16 Concept 11.1 Several Strategies Are Used to Regulate Gene Expression Host cells have systems to repress the invading viral genes. One system uses transcription terminator proteins that interfere with RNA polymerase. HIV counteracts this negative regulation with Tat (Transactivator of transcription), which allows RNA polymerase to transcribe the viral genome.

17 Figure 11.5 Regulation of Transcription by HIV (Part 1)

18 Figure 11.5 Regulation of Transcription by HIV (Part 2)

19 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons Prokaryotes conserve energy by making proteins only when needed. In a rapidly changing environment, the most efficient gene regulation is at the level of transcription. E. coli must adapt quickly to food supply changes. Glucose or lactose may be present.

20 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons Uptake and metabolism of lactose involve three proteins: -galactoside permeasea carrier protein that moves sugar into the cell -galactosidasean enzyme that hydrolyses lactose -galactoside transacetylasetransfers acetyl groups to certain -galactosides If E. coli is grown with glucose but no lactose present, no enzymes for lactose conversion are produced.

21 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons If lactose is predominant and glucose is low, E. coli synthesizes all three enzymes. If lactose is removed, synthesis stops. A compound that induces protein synthesis is an inducer. Gene expression and regulating enzyme activity are two ways to regulate a metabolic pathway.

22 Figure 11.6 Two Ways to Regulate a Metabolic Pathway

23 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons Structural genes specify primary protein structurethe amino acid sequence. The three structural genes for lactose enzymes are adjacent on the chromosome, share a promoter, and are transcribed together. Their synthesis is all-or-none.

24 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons A gene cluster with a single promoter is an operonthe one that encodes for the lactose enzymes is the lac operon. An operator is a short stretch of DNA near the promoter that controls transcription of the structural genes. Inducible operonturned off unless needed Repressible operonturned on unless not needed

25 Figure 11.7 The lac Operon of E. coli

26 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons The lac operon is only transcribed when a -galactoside predominates in the cell: A repressor protein is normally bound to the operator, which blocks transcription. In the presence of a -galactoside, the repressor detaches and allows RNA polymerase to initiate transcription. The key to this regulatory system is the repressor protein.

27 Figure 11.8 The lac Operon: An Inducible System (Part 1)

28 Figure 11.8 The lac Operon: An Inducible System (Part 2)

29 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons A repressible operon is switched off when its repressor is bound to its operator. However, the repressor only binds in the presence of a co-repressor. The co-repressor causes the repressor to change shape in order to bind to the promoter and inhibit transcription. Tryptophan functions as its own co- repressor, binding to the repressor of the trp operon.

30 Figure 11.9 The trp Operon: A Repressible System (Part 1)

31 Figure 11.9 The trp Operon: A Repressible System (Part 2)

32 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons Difference in two types of operons: In inducible systemsa metabolic substrate (inducer) interacts with a regulatory protein (repressor); the repressor cannot bind and allows transcription. In repressible systemsa metabolic product (co-repressor) binds to regulatory protein, which then binds to the operator and blocks transcription.

33 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons Generally, inducible systems control catabolic pathwaysturned on when substrate is available Repressible systems control anabolic pathwaysturned on until product concentration becomes excessive

34 Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons Sigma factorsother proteins that bind to RNA polymerase and direct it to specific promoters Global gene regulation: Genes that encode proteins with related functions may have a different location but have the same promoter sequencethey are turned on at the same time. Sporulation occurs when nutrients are depletedgenes are expressed sequentially, directed by a sigma factor.

35 Table 11.1 Transcription in Bacteria and Eukaryotes

36 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Transcription factors act at eukaryotic promoters. Each promoter contains a core promoter sequence where RNA polymerase binds. TATA box is a common core promoter sequencerich in A-T base pairs. Only after general transcription factors bind to the core promoter, can RNA polymerase II bind and initiate transcription.

37 Figure The Initiation of Transcription in Eukaryotes (Part 1)

38 Figure The Initiation of Transcription in Eukaryotes (Part 2)

39 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Besides the promoter, other sequences bind regulatory proteins that interact with RNA polymerase and regulate transcription. Some are positive regulatorsactivators; others are negativerepressors. DNA sequences that bind activators are enhancers, those that bind repressors are silencers. The combination of factors present determines the rate of transcription.

40 In-Text Art, Ch. 11, p. 216

41 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Transcription factors recognize particular nucleotide sequences: NFATs (nuclear factors of activated T cells) are transcription factors that control genes in the immune system. They bind to a recognition sequence near the genes promoters. The binding produces an induced fitthe protein changes conformation.

42 Figure A Transcription Factor Protein Binds to DNA

43 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Gene expression can be coordinated, even if genes are far apart on different chromosomes. They must have regulatory sequences that bind the same transcription factors. Plants use this to respond to droughtthe scattered stress response genes each have a specific regulatory sequence, the dehydration response element. During drought, a transcription factor changes shape and binds to this element.

44 Figure Coordinating Gene Expression

45 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Gene transcription can also be regulated by reversible alterations to DNA or chromosomal proteins. Alterations can be passed on to daughter cells. These epigenetic changes are different from mutations, which are irreversible changes to the DNA sequence.

46 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Some cytosine residues in DNA are modified by adding a methyl group covalently to the 5 carbonforms 5- methylcytosine DNA methyltransferase catalyzes the reactionusually in adjacent C and G residues. Regions rich in C and G are called CpG islandsoften in promoters

47 Figure DNA Methylation: An Epigenetic Change (Part 1)

48 Figure DNA Methylation: An Epigenetic Change (Part 2)

49 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes This covalent change in DNA is heritable: When DNA replicates, a maintenance methylase catalyzes formation of 5- methylcytosine in the new strand. However, methylation pattern may be altereddemethylase can catalyze the removal of the methyl group.

50 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Effects of DNA methylation: Methylated DNA binds proteins that are involved in repression of transcription genes tend to be inactive (silenced). Patterns of DNA methylation may include large regions or whole chromosomes.

51 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Two kinds of chromatin are visible during interphase: Euchromatindiffuse and light-staining; contains DNA for mRNA transcription Heterochromatincondensed, dark- staining; contains genes not transcribed

52 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes A type of heterochromatin is the inactive X chromosome in mammals. Males (XY) and females (XX) contain different numbers of X-linked genes, yet for most genes transcription, rates are similar. Early in development, one of the X chromosomes is inactivatedthis Barr body is identifiable during interphase and can be seen in cells of human females.

53 Figure X Chromosome Inactivation

54 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Another mechanism for epigenetic regulation is chromatin remodeling, or the alteration of chromatin structure. Nucleosomes contain DNA and positively- charged histones in a tight complex, inaccessible to RNA polymerase. Histone acetyltransferases change the charge by adding acetyl groups to the amino acids on the histones tail.

55 In-Text Art, Ch. 11, p. 219 (1)

56 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes The change in charge opens up the nucleosomes as histone loses its affinity for DNA. More chromatin remodeling proteins bind and open the DNA for gene expression. Thus, histone acetyltransferases can activate transcription.

57 Figure Epigenetic Remodeling of Chromatin for Transcription

58 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Histone deacetylase is another kind of chromatin remodeling protein. It can remove the acetyl groups from the histones, repressing transcription.

59 Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors and DNA Changes Environment plays an important role in epigenetic modifications. Even though they are reversible, some epigenetic changes can permanently alter gene expression patterns. If the cells form gametes, the epigenetic changes can be passed on to the next generation. Monozygotic twins show different DNA methylation patterns after living in different environments.

60 Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription Eukaryotic gene expression can be regulated after the initial gene transcript is made. Different mRNAs can be made from the same gene by alternative splicing. As introns and exons are spliced out, new proteins are made. This may be a deliberate mechanism for generating proteins with different functions, from a single gene.

61 Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription Examples of alternative splicing: The HIV genome encodes nine proteins, but is transcribed as a single pre-mRNA. In Drosophila the Sxl gene with four exons is spliced differently to produce different combinations in males and females.

62 Figure Alternative Splicing Results in Different Mature mRNAs and Proteins

63 Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription MicroRNAs(miRNAs)small molecules of noncoding RNAare important regulators of gene expression. In C. elegans, lin-14 mutations cause the larvae to skip the first stagethus the normal role for lin-14 is to be involved in stage one of development. lin-4 mutations cause cells to repeat stage one eventsthus the normal role for lin-4 is to negatively regulate lin-14, so that cells can progress to the next stage of development.

64 Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription lin-4 encodes not for a protein but for a 22- base miRNA that inhibits lin-14 expression posttranscriptionally by binding to its mRNA. Many miRNAs have been describedonce transcribed they are guided to a target mRNA to inhibit its translation and to degrade the mRNA.

65 Figure mRNA Degradation Caused by MicroRNAs

66 Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription mRNA translation can be regulated. Protein and mRNA concentrations are not consistently related governed by factors acting after mRNA is made. Cells either block mRNA translation or alter how long new proteins persist in the cell.

67 Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after Transcription Three ways to regulate mRNA translation: Inhibition of translation with miRNAs Modification of the 5 cap end of mRNA can be modified if cap is unmodified mRNA is not translated. Repressor proteins can block translation directlytranslational repressors

68 Figure A Repressor of Translation

69 Figure A Proteasome Breaks Down Proteins

70 Answer to Opening Question The CREB family of transcription factors can activate or repress gene expression by binding to the cAMP response element (CRE) sequence found in the promoter region of many genes. CREB binding is essential in many organs, including the brain, and has been linked to addiction and memory tasks as well as to metabolism.

71 Figure An Explanation for Alcoholism?


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