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Behavioral epigenetics studies heritable gene expression changes without DNA sequence alterations. Explore prokaryotic gene regulation efficiency, operon control mechanisms, and metabolic pathway regulation with practical examples.
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16 Regulation of Gene Expression 16.1 How Is Gene Expression Regulated in Prokaryotes? 16.2 How Is Eukaryotic Gene Transcription Regulated? 16.3 How Do Viruses Regulate Their Gene Expression? 16.4 How Do Epigenetic Changes Regulate Gene Expression? 16.5 How Is Eukaryotic Gene Expression Regulated After Transcription?
16 Regulation of Gene Expression Behavioral epigenetics: study of heritable changes in gene expression that do not involve changes in the DNA sequence. Methylation of some gene promoters may result from high levels of stress, and inhibit gene transcription. Methylation in the glucocorticoid receptor gene may result in behavioral problems. Opening Question: Can epigenetic changes be manipulated?
16.1 How Is Gene Expression Regulated in Prokaryotes? Prokaryotes can make some proteins only when they are needed. To shut off supply of a protein, the cell can: • Downregulate mRNA transcription • Hydrolyze mRNA, preventing translation • Prevent mRNA translation at the ribosome • Hydrolyze the protein after it is made • Inhibit the protein’s function
16.1 How Is Gene Expression Regulated in Prokaryotes? The earlier the cell can stop protein synthesis, the less energy is wasted. Blocking transcription is more efficient than transcribing the gene, translating the message, and then degrading or inhibiting the protein.
16.1 How Is Gene Expression Regulated in Prokaryotes? Gene expression begins at the promoter. Two types of regulatory proteins can bind to promoters: • Negative regulation—a repressor protein prevents transcription • Positive regulation—an activator protein stimulates transcription
16.1 How Is Gene Expression Regulated in Prokaryotes? E. coli in the human intestine must adjust quickly to changes in food supply. Glucose is the easiest sugar to metabolize. Lactose is β-galactoside (disaccharide of galactose and glucose).
16.1 How Is Gene Expression Regulated in Prokaryotes? Three proteins are need for the uptake and metabolism of lactose. • -galactoside permease—carrier protein that moves lactose into the cell • -galactosidase—hydrolyses lactose • -galactoside transacetylase—transfers acetyl groups from acetyl CoA to certain -galactosides
16.1 How Is Gene Expression Regulated in Prokaryotes? If E.coli is grown with glucose but no lactose, no enzymes for lactose conversion are produced. If lactose is predominant and glucose is low, E.coli synthesizes all three enzymes after a short lag period.
Figure 16.2 An Inducer Stimulates the Expression of a Gene for an Enzyme
16.1 How Is Gene Expression Regulated in Prokaryotes? During the lag period, mRNA for β-galactosidase is produced. If lactose is removed, the mRNA level goes down.
16.1 How Is Gene Expression Regulated in Prokaryotes? Compounds that stimulate protein synthesis are called inducers; The proteins are inducible proteins. Constitutiveproteins are made at a constant rate.
16.1 How Is Gene Expression Regulated in Prokaryotes? Metabolic pathways can be regulated in two ways: • Allosteric regulation of enzyme-catalyzed reactions allows rapid fine-tuning • Regulation of protein synthesis is slower but conserves energy and resources. Protein synthesis requires a lot of energy
16.1 How Is Gene Expression Regulated in Prokaryotes? Structural genes specify primary protein structure—the amino acid sequence. The 3 structural genes for lactose enzymes are adjacent on the chromosome and share a promoter, forming the lac operon.
16.1 How Is Gene Expression Regulated in Prokaryotes? An operon is a gene cluster with a single promoter. A typical operon consists of: • A promoter • Two or more structural genes • An operator—a short sequence between the promoter and the structural genes; binds to regulatory proteins
16.1 How Is Gene Expression Regulated in Prokaryotes? Three ways to control operon transcription: • An inducible operon regulated by a repressor protein • A repressible operon regulated by a repressor protein • An operon regulated by an activator protein
16.1 How Is Gene Expression Regulated in Prokaryotes? In the lac operon the operator can bind a repressor protein, which blocks transcription. The repressor has 2 binding sites: one for the operator, and one for the inducer (lactose). When lactose is absent, the repressor prevents binding of RNA polymerase to the promoter.
16.1 How Is Gene Expression Regulated in Prokaryotes? When lactose is present, it binds to the repressor and changes the repressor’s shape. This prevents the repressor from binding to the operator, and then RNA polymerase can bind to the promoter, and the genes are transcribed.
16.1 How Is Gene Expression Regulated in Prokaryotes? Other E. coli systems are repressible—the operon is turned on unless repressed under specific conditions. In these systems, the repressor isn’t bound to the operator until a co-repressor binds to it. The repressor then changes shape, binds to the operator, and blocks transcription.
16.1 How Is Gene Expression Regulated in Prokaryotes? The trp operon is a repressible system. The genes code for enzymes that catalyze synthesis of tryptophan. When there is enough tryptophan in the cell, tryptophan binds to the repressor, which then binds to the operator. Tryptophan is the co-repressor.
16.1 How Is Gene Expression Regulated in Prokaryotes? Inducible systems: metabolic substrate (inducer) interacts with a regulatory protein (repressor); repressor can’t bind to operator and transcription proceeds. Repressible systems: a metabolic product (co-repressor) binds to a regulatory protein, which then binds to the operator and blockstranscription.
16.1 How Is Gene Expression Regulated in Prokaryotes? Inducible systems control catabolic pathways—they are turned on when substrate is available. Repressible systems control anabolic pathways—they are turned on until product concentration becomes excessive.
16.1 How Is Gene Expression Regulated in Prokaryotes? Positive control: an activator protein can increase transcription. If glucose and lactose levels are both high, the lac operon is not transcribed efficiently. Efficient transcription requires binding of an activator protein to its promoter.
16.1 How Is Gene Expression Regulated in Prokaryotes? If glucose levels are low, a signaling pathway leads to increased levels of cyclic AMP. cAMP binds to cAMP receptor protein (CRP); conformational change in CRP allows it to bind to the lac promoter. CRP is an activator of transcription; its binding results in more efficient binding of RNA polymerase and thus increased transcription.
16.1 How Is Gene Expression Regulated in Prokaryotes? If glucose is abundant, CRP does not bind to the lac operon promoter and efficiency of transcription is reduced. This is catabolite repression, a system of gene regulation in which presence of a preferred energy source represses other catabolic pathways.
16.1 How Is Gene Expression Regulated in Prokaryotes? Promoters bind and orient RNA polymerase so that the correct DNA strand is transcribed. All promoters have consensus sequences that allow them to be recognized by RNA polymerase. Different classes of consensus sequences are recognized by regulatory proteins called sigma factors.
16.1 How Is Gene Expression Regulated in Prokaryotes? Sigma factors bind to RNA polymerase and direct it to certain promoters. Genes for proteins with related functions may be at different locations in the genome, but share consensus sequences and can be recognized by sigma factors.
16.1 How Is Gene Expression Regulated in Prokaryotes? Sigma-70 factor is active most of the time and binds to consensus sequences of housekeeping genes (genes normally expressed in actively growing cells). Others are activated only under specific conditions.
16.2 How Is Eukaryotic Gene Transcription Regulated? In development of multicellular organisms, certain proteins must be made at just the right times and in just the right cells. The expression of eukaryotic genes must be precisely regulated. Regulation can occur at several different points.
Figure 16.7 Potential Points for the Regulation of Gene Expression (Part 1)
Figure 16.7 Potential Points for the Regulation of Gene Expression (Part 2)
16.2 How Is Eukaryotic Gene Transcription Regulated? Both prokaryotes and eukaryotes use DNA-protein interactions and negative and positive control to regulate gene expression. But there are differences, some dictated by the presence of a nucleus, which physically separates transcription and translation.
16.2 How Is Eukaryotic Gene Transcription Regulated? Eukaryote promoters contain a sequence called the TATA box—where DNA begins to denature. Promoters also include regulatory sequences recognized by transcription factors (regulatory proteins).
16.2 How Is Eukaryotic Gene Transcription Regulated? RNA polymerase II can only bind to the promoter after general transcription factors have assembled on the chromosome: TFIID binds to TATA box; then other factors bind to form an initiation complex.
Figure 16.8 The Initiation of Transcription in Eukaryotes (Part 1)
Figure 16.8 The Initiation of Transcription in Eukaryotes (Part 2)
16.2 How Is Eukaryotic Gene Transcription Regulated? Some regulatory sequences are common to promoters of many genes, such as the TATA box. Some sequences are specific to a few genes and are recognized by transcription factors found only in certain tissues. These play an important role in cell differentiation.
16.2 How Is Eukaryotic Gene Transcription Regulated? Enhancers: regulatory sequences that bind transcription factors that activate transcription or increase rate of transcription. Silencers: bind transcription factors that repress transcription.
16.2 How Is Eukaryotic Gene Transcription Regulated? Most regulatory sequences are located near the transcription start site. Others may be located thousands of base pairs away. Transcription factors may interact with the RNA polymerase complex and cause the DNA to bend.
Figure 16.9 Transcription Factors and Transcription Initiation
16.2 How Is Eukaryotic Gene Transcription Regulated? Often there are many transcription factors involved. The combination of factors present determines the rate of transcription. Although the same genes are present in all cells, the fate of the cell is determined by which of its genes are expressed.
