Control of Gene Expression in Bacteria Benjamin A. Pierce GENETICS A Conceptual Approach FIFTH EDITION CHAPTER 17 Control of Gene Expression in Bacteria © 2014 W. H. Freeman and Company 1

Changes in a relatively small number of regulatory sequences help produce the large phenotypic differences between humans and chimpanzees.

17.1 Eukaryotic Cells and Bacteria Have Many Features of Gene Regulation in Common, but They Differ in Several Important Ways Each structural gene has its own promoter, and is transcribed separately. DNA must unwind from the histone proteins before transcription. Transcription and translation are separated in time and space.

17.2 Changes in Chromatin Structure Affect the Expression of Genes DNase I hypersensitivity DNase I hypersensitive sites: more open chromatin configuration site, upstream of the transcription start site Histone modification Addition of methyl groups to the histone protein tails Addition of acetyl groups to histone proteins

Figure 17.1 Chromatin remodeling complexes reposition the nucleosomes, allowing transcription factors and RNA polymerase to bind to promoters and initiate transcription.

Figure 17.2 The acetylation of histone proteins alters chromatin structure and permits some transcription factors to bind to DNA.

17.2 Changes in Chromatin Structure Affect the Expression of Genes Acetylation of histones controls flowering in Arabidopsis Flowering locus C (FLC) gene Flowering locus D (FLD) gene

Figure 17.3 Flowering in Arabidopsis is controlled in part by FLD, a gene that encodes a deacetylase enzyme. This enzyme removes acetyl groups from histone proteins in chromatin surrounding FLC, a gene that suppresses flowering. The removal of the acetyl groups from the histones restores chromatin structure and represses the transcription of FLC, thereby allowing the plant to flower.

17.2 Changes in Chromatin Structure Affect the Expression of Genes Chromatin remodeling Chromatin-remodeling complexes: bind directly to DNA sites and reposition nucleosomes DNA Methylation DNA methylation of cytosine bases adjacent to guanine nucleotides (CpG)–CpG islands

Figure 17.4 Chromatin immunoprecipitation (ChIP) can be used to identify DNA-binding sites of a specific protein and the locations of modified histone proteins.

The Initiation of Transcription Is Regulated by Transcription Factors and Regulator Proteins Transcriptional Activators and Coactivators Stimulate and stabilize basal transcription apparatus at core promoter Mediator Regulation of galactose metabolism through GAL4

Figure 17.5 Transcriptional activator proteins bind to sites on DNA and stimulate transcription. Most act by stimulating or stabilizing the assembly of the basal transcription apparatus.

Figure 17.6 The consensus sequences in the promoters of three eukaryotic genes illustrate the principle that different sequences can be mixed and matched in different combinations. A different transcriptional activator protein binds to each consensus sequence, and so each promoter responds to a unique combination of activator proteins.

Figure 17.7 Transcription is activated by GAL4 in response to galactose. GAL4 binds to the UASG site and controls the transcription of genes in galactose metabolism.

The Initiation of Transcription Is Regulated by Transcription Factors and Regulator Proteins Transcriptional Repressors Bind to silencers Enhancers and Insulators Enhancer: DNA sequence stimulating transcription from a distance away from promoter Insulator: DNA sequence that blocks or insulates the effect of enhancers

Figure 17.8 An insulator blocks the action of an enhancer on a promoter when the insulator lies between the enhancer and the promoter.

Concept Check 1 Most transcriptional activator proteins affect transcription by interacting with . introns the basal transcription apparatus DNA polymerase nucleosomes

Concept Check 1 Most transcriptional activator proteins affect transcription by interacting with . introns the basal transcription apparatus DNA polymerase nucleosomes

Figure 17.9 Multiple response elements (MREs) are found in the upstream region of the metallothionein gene. The basal transcription apparatus binds near the TATA box. In response to heavy metals, activator proteins bind to several MREs and stimulate transcription. The TRE response element is the binding site for transcription factor AP1, which is stimulated by phorbol esters. In response to glucocorticoid hormones, steroid-receptor proteins bind to the GRE response element located approximately 250 nucleotides upstream of the metallothionein gene and stimulate transcription.

The Initiation of Transcription Is Regulated by Transcription Factors and Regulator Proteins Regulation of Transcriptional Stalling and Elongation Heat shock proteins Coordinated gene regulation Response elements: common regulatory elements upstream of the start sites of a collective group of genes in response to a common environmental stimulus

17.4 Some Genes Are Regulated by RNA Processing and Degradation Gene regulation through RNA splicing Alternative splicing in the T-antigen gene Alternative splicing in Drosophila sexual development

Figure 17.10 Alternative splicing leads to the production of the small t antigen and the large T antigen in the mammalian virus SV40.

Figure 17.11 Alternative splicing controls sex determination in Drosophila.

Figure 17. 12 Alternative splicing of tra pre-mRNA Figure 17.12 Alternative splicing of tra pre-mRNA. Two alternative 3′ splice sites are present.

17.4 Some Genes Are Regulated by RNA Processing and Degradation The Degradation of RNA 5′-cap removal Shortening of the poly(A) tail Degradation of 5′ UTR, coding sequence, and 3′ UTR

17.5 RNA Interference Is an Important Mechanism of Gene Regulation Small interfering RNAs and microRNAs Dicer RISC: RNA-induced silencing complex

Figure 17.13 RNA silencing leads to the degradation of mRNA or to the inhibition of translation or transcription.

17.5 RNA Interference Is an Important Mechanism of Gene Regulation Mechanisms of Gene Regulation by RNA interference RNA cleavage: RISC containing an siRNA, pair with mRNA molecules and cleavage to the mRNA Inhibition of translation Transcriptional silencing: altering chromatin structure Silencer-independent degradation of mRNA

Concept Check 2 In RNA silencing, siRNAs and miRNAs usually bind to which part of the mRNA molecules that they control? 5′ UTR the segment that encodes amino acids 3′ poly (A) tail 3′ UTR

Concept Check 2 In RNA silencing, siRNAs and miRNAs usually bind to which part of the mRNA molecules that they control? 5′ UTR the segment that encodes amino acids 3′ poly (A) tail 3′ UTR

17.6 Some Genes Are Regulated by Processes That Affect Translation or by Modification of Proteins Proteins bind 5′ UTR Affect availability of translational machinery

Figure 17.14 The expression of some eukaryotic genes is regulated by the availability of components required for translation. In this example, exposure to an antigen stimulates an increased availability of initiation factors and a subsequent increase in protein synthesis, leading to T-cell proliferation.