Chapter 19 Summary
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Core Concepts Summary
19.1 The regulation of gene expression in eukaryotes takes place at many levels, including DNA packaging in chromosomes, transcription, and RNA processing.
Gene expression involves the turning on or turning off of a gene. page 378
Gene regulation determines where, when, how much, and which gene product is made. page 378
Regulation at the level of chromatin involves chemical modifications of DNA and histones that make a gene accessible or inaccessible to the transcriptional machinery. page 378
Dosage compensation is the process by which the expression of X-
X-
X-
Transcriptional regulation controls whether or not transcription of a gene occurs. page 382
Transcription can be regulated by regulatory transcription factors that bind to specific DNA sequences known as enhancers that can be near, in, or far from genes. page 382
Further levels of regulation after a gene is transcribed to mRNA include RNA processing, splicing, and editing. page 383
19.2 After an mRNA is transcribed and exported to the cytoplasm in eukaryotes, gene expression can be regulated at the level of mRNA stability, translation, and posttranslational modification of proteins.
Small regulatory RNAs, especially microRNA (miRNA) and small interfering RNA (siRNA), affect gene expression through their effects on translation or mRNA stability. page 384
Translational regulation controls the rate, timing, and location of protein synthesis. page 384
Translational regulation is determined by many features of an mRNA molecule, including the 5′ and 3′ UTR, the cap, and the poly(A) tail. page 385
Posttranslational modification comes into play after a protein is synthesized, and includes chemical modification of side groups of amino acids, affecting the structure and activity of a protein. page 385
Gene regulation is influenced by both genetic and environmental factors. page 386
19.3 Transcriptional regulation is illustrated in bacteria by the control of the production of proteins needed for the utilization of lactose, and in viruses by the control of the lytic and lysogenic pathways.
Transcriptional regulation can be positive, in which a gene is usually off and is turned on in response to the binding to DNA of a regulatory protein called an activator, or negative, in which a gene is usually on and is turned off in response to the binding to DNA of a regulatory protein called a repressor. page 387
Jacob and Monod studied the lactose operon in E. coli as a model for bacterial gene regulation. page 388
When lactose is added to culture of bacteria, the genes for the uptake of lactose (permease, encoded by lacY) and cleavage of lactose (β-galactosidase, encoded by lacZ) are expressed. page 388
The lactose operon is negatively regulated by the repressor protein (encoded by lacI), which binds to a DNA sequence known as the operator. page 389
When lactose is added to the medium, it induces an allosteric change in the repressor protein, preventing it from binding to the operator and allowing transcription of lacY and lacZ. In this way, lactose acts as an inducer of the lactose operon. page 390
An additional level of regulation of the lactose operon is provided by the CRP–
The lytic and lysogenic pathways of bacteriophage λ have also been well studied as a model of gene regulation. page 392
When bacteriophage λ infects E. coli, it can lyse the cell (the lytic pathway) or its DNA can become integrated into the bacterial genome (the lysogenic pathway). page 392
In infection of E. coli cells by bacteriophage λ, predominance of cro protein results in the lytic pathway, whereas predominance of the cI protein results in the lysogenic pathway. page 392
Self-Assessment
Distinguish between gene expression and gene regulation.
Self-Assessment 1 Answer
Gene expression is when genes are turned on, and gene regulation controls when, where, and how much gene expression happens. Gene regulation makes sure that the gene is turned on in the right place at the right time in the right amount.
Explain what is meant by different “levels” of gene regulation and give some examples.
Self-Assessment 2 Answer
Gene regulation can occur at each level of gene expression. For example, gene expression can be regulated at the level of transcription by means of DNA methylation or the modification of chromosomal proteins that alter chromatin structure and nucleosome positioning to either block or permit access of the transcriptional machinery to genes. Gene expression can be regulated at the level of RNA processing through alternative splicing, RNA editing, or transport of mRNA out of the nucleus. Gene expression can be regulated at the level of translation by altering the efficiency of translation initiation, the stability of the mRNA, or through small regulatory RNAs. Gene expression can be regulated at the level of posttranslation by mechanisms including protein phosphorylation or other covalent modifications.
Give two examples of how DNA bases and chromatin can be modified to regulate gene expression, and explain why these kinds of modifications result in increased or decreased gene expression.
Self-Assessment 3 Answer
Bases can be modified by attaching a methyl group to cytosine. When several cytosines are methylated in close proximity, it creates a methylated CpG island. When a methylated CpG island is near a promoter region, that gene is usually repressed or turned off. DNA in a cell is wrapped around an octamer of histone proteins. When DNA is coiled tightly around the histones, the DNA is not accessible to transcription proteins. However, when the chromatin unravels from the histone through histone modifications, the transcription proteins can access the DNA and begin transcribing it. DNA in a cell is also associated with proteins to make a DNA‒protein complex called chromatin. Chromatin remodeling allows or prevents access of transcription factors to DNA.
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Explain how X-
inactivation in female mammals results in patchy coat color in calico cats. Self-Assessment 4 Answer
The level of expression of X-linked genes is the same for both sexes as a result of inactivation of one of the two X chromosomes in female cells (XX). This phenomenon is called X-inactivation and is a means of dosage compensation. Thus, females are actually a mosaic of tissues: In some cells the maternal X is expressed, and in other cells the paternal X is expressed. In calico cats, which are always female, the orange and black fur color is due to different alleles of a single gene in the X chromosome. Based on which X chromosome is active, the cat will have patches of color in specific areas.
Explain how one protein-
coding gene can code for more than one polypeptide chain. Self-Assessment 5 Answer
One protein-
coding gene can code for more than one polypeptide chain through the mechanism of alternative splicing. By leaving in various exons or splicing them out, the spliceosome can splice the mRNA in different ways to yield different proteins. A second mechanism that produces more than one protein from a single gene involves RNA editing. RNA editing is a process in which individual bases in mRNA are altered. In some cases, individual amino acids in a protein, and therefore potentially the entire structure or function of the protein, can be changed by RNA editing. Name and describe three ways in which gene expression can be influenced after mRNA is processed and leaves the nucleus.
Self-Assessment 6 Answer
One way in which gene expression can be influenced after mRNA is processed and leaves the nucleus is through the actions of small regulatory RNAs that can either inhibit translation or degrade mRNA. A second way is to alter the 5'cap of the mRNA, so translation initiation cannot occur. Altering or deleting the poly(A) tail is a third way in which translation of the mRNA can be inhibited.
Diagram the lactose operon in E. coli with the proper order of the elements lacI, lacO, lacY, and lacZ, and explain how expression is controlled in the presence and in the absence of lactose.
Self-Assessment 7 Answer
Expression is controlled by allolactose, an isomer of lactose that is present whenever lactose is present. Allolactose binds to the repressor encoded by lacI when lactose is present, preventing the repressor from binding to the lactose operator. When the repressor protein is not bound to the operator, lacZ and lacY are transcribed as a polycistronic mRNA. When lactose, and therefore allolactose, are not present in the cell, the repressor protein is free to bind to the operator, preventing transcription. Lactose (acting through its isomer allolactose) is therefore an inducer of the lactose operon.
Describe the role of the CRP–
cAMP complex in positive regulation of the lactose operon in E. coli. Self-Assessment 8 Answer
The CRP-
cAMP complex helps regulate which carbohydrates are utilized first by the bacterium. In the absence of glucose, E.coli’s preferred energy source, cAMP levels are high and the CRP- cAMP complex binds to a site near the promoter of the lac operon and activates transcription. In the presence of glucose, cAMP levels are low and the CRP- cAMP complex does not bind, and transcription is not induced to high levels even in the presence of lactose. Describe what is meant by lysis and lysogeny, and explain how gene regulation controls these two pathways.
Self-Assessment 9 Answer
Lysis is the process in which a cell bursts open to release progeny phage. Lysogeny is the process in which the phage DNA is incorporated into the bacterial chromosome. In the lytic pathway, the phage protein cro is produced and inhibits access to the promoter PM, thereby blocking expression of cI. This allows for the transcription of genes in the lytic pathway to take place. In the lysogeny pathway, the protein cl is produced, which prevents the translation of cro and cll proteins. This action shuts down the translation of all genes not associated with lysogeny.
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