Dynamic Study Module Ch. 19
What is the tightly coiled DNA-protein complex?
Chromatin
How can gene expression change in an individual cell in a multicellular eukaryotic organism? The expression of specific genes is turned on or off by signal pathways activated by molecules secreted by nearby or distant cells. All of the genes in the cell are translated, but only some of the resulting proteins are functional at any given time. DNA must be tightly coiled into chromosomes for transcription to occur. Gene transcription is regulated primarily by the presence or absence of specific nutrients.
The expression of specific genes is turned on or off by signal pathways activated by molecules secreted by nearby or distant cells. *If a signal that says "becomes a muscle cell" reaches a cell in the early embryo, it triggers a signal transduction cascade that leads to the production of transcription factors specific to muscle cells. Because different transcription factors bind to specific regulatory sequences, they turn on the production of muscle-specific proteins. But if no "become-a-muscle-cell" signal arrives, then no muscle-specific transcription factors are produced and no muscle-specific gene expression takes place.
Which of the following will speed up the rate of transcription? Repressors Coactivators Basal transcription factors Activators
Activators *Activators bind to enhancers to increase the rate of transcription. Repressors bind to silencers to slow the rate of transcription. Coactivators integrate signals from activators. Basal transcription factors place RNA polymerase at the start of transcription to begin the transcription process.
Which of the following is true about the initiation of transcription of mRNA in eukaryotes? Basal transcription factors that bind the promoter and regulatory transcription factors that bind the enhancer are connected by mediators to initiate transcription. Basal transcription factors that bind the promoter and regulatory transcription factors that bind the enhancer are connected by sigma factors to initiate transcription. Basal transcription factors that bind the promoter interact with histones to initiate transcription. Basal transcription factors that bind the enhancer and regulatory transcription factors that bind the promoter are connected by coactivators to initiate transcription.
Basal transcription factors that bind the promoter and regulatory transcription factors that bind the enhancer are connected by mediators to initiate transcription. *Step 1: Transcriptional activators bind to DNA and recruit chromatin-remodeling complexes and histone acetyltransferases (HATs). Step 2: The chromatin-remodeling complexes and HATs open a swath of chromatin that includes the promoter, promoter proximal elements, and enhancers. Step 3: Other transcriptional activators bind to the newly exposed enhancers and promoter-proximal elements; basal transcription factors bind to the promoter and recruit RNA polymerase II. Step 4: Mediator connects the transcriptional activators and basal transcription factors that are bound to DNA. This step is made possible through DNA looping. RNA polymerase II can now begin transcription.
Which of the following statements is generally true of cancer? Cancer always occurs when DNA is damaged. Cancer always occurs when tumor suppressor genes are mutated. Cancer occurs when mutations disable genes that stop the cell cycle or those that activate it. Cancer only occurs when a protein that activates the cell cycle is constitutively expressed.
Cancer occurs when mutations disable genes that stop the cell cycle or those that activate it. *Each type of cancer is caused by a different set of mutations that lead to cancer when they affect one of two classes of genes: (1) genes that stop or slow the cell cycle, and (2) genes that trigger cell growth and division by initiating specific phases in the cell cycle. Many of the genes that are mutated in cancer influence gene regulation. There are several mechanisms to repair damaged DNA therefore cancer does not always occur when DNA is damaged. Proteins that stop or slow the cell cycle when conditions are unfavorable for cell division are called tumor suppressors. Logically enough, the genes that code for these proteins are called tumor suppressor genes. If the function of a tumor suppressor gene is lost because of mutation, then a key brake on the cell cycle is eliminated. However, a mutation in the tumor suppressor gene does not always lead to cancer. Uncontrolled cell growth may result when a mutation in a regulatory gene creates a protein that activates the cell cycle constitutively. However, a protein that activates the cell cycle is not the only cause of cancer.
How can 2 meters of DNA found in a typical human cell be packed into a nucleus that is only a few micrometers in diameter? Nucleic acids have an intrinsic affinity for proteins and are bound closely to all of the proteins in the cell. DNA is associated tightly with histone proteins in nucleosomes, which pack the DNA compactly. The DNA molecules are normally single-stranded. Eukaryotic nuclei are expandable and enlarge to accommodate the long DNA molecules.
DNA is associated tightly with histone proteins in nucleosomes, which pack the DNA compactly.
In studies of chromatin and nucleosomes, how was DNase used to show that open chromatin structures are transcriptionally active? DNA not wrapped around histones is not transcribed but is susceptible to degradation by DNase. DNA that is not condensed into chromatin is transcribed and also protected from DNase degradation. DNA wrapped around histones is not transcribed and is protected from degradation by nucleases. Only single-stranded DNA is transcriptionally active and can be broken down by nucleases.
DNA wrapped around histones is not transcribed and is protected from degradation by nucleases. *DNases are enzymes that cut DNA. Some DNases cleave DNA at random locations, and these cannot cut efficiently if DNA is tightly wrapped with proteins. As the figure shows, this type of DNase works effectively only if DNA is in a decondensed configuration. Harold Weintraub and Mark Groudine used this observation to test the hypothesis that the DNA of actively transcribed genes is in an open configuration. In chicken blood cells, they compared chromatin structure in two genes: β-globin and ovalbumin. β-globin is a protein that is part of the hemoglobin found in red blood cells; ovalbumin is a protein found in egg white. In blood cells, the β-globin gene is transcribed at high levels, but the ovalbumin gene is not transcribed at all. After treating blood cells with DNase and then analyzing the state of chromatin at the β-globin and ovalbumin genes, the researchers found that DNase cut the β-globin gene DNA much more readily than DNA of the ovalbumin gene. They interpreted this finding as evidence that in blood cells, chromatin of the actively transcribed β-globin gene was decondensed; and conversely, chromatin of the non-transcribed ovalbumin gene was condensed. Studies using DNase on different genes in different cell types yielded similar results.
What are two mechanisms used for turning genes off in eukaryotic cells? Genes are turned off when chromatin is in an open conformation or when a regulatory protein binds to a silencer. Genes are turned off when chromatin remains condensed or a regulatory protein binds to an enhancer. Genes are turned off when the chromatin is in an open conformation or a regulatory protein binds to an enhancer. Genes are turned off when chromatin remains condensed or a regulatory protein binds to a silencer.
Genes are turned off when chromatin remains condensed or a regulatory protein binds to a silencer. ***Chromatin Remodeling*** condensed- (HDAC; acetyl group removed), genes inactive, genes can not be transcribed decondensed- (HAT;acetyl group added), genes active, genes can be transcribed
Which of the following events would most likely increase production of a growth hormone protein? Increased production of proteolytic enzymes Increased mRNA transcription Increased mRNA degradation Increased concentration of growth hormone in the cell
Increased mRNA transcription * Although gene expression can be controlled at many levels, regulating the start of transcription is at center stage. Getting RNA polymerase to initiate transcription requires interactions between many proteins, including transcriptional activators that are bound to enhancers and promoter-proximal elements, mediator, basal transcription factors, and RNA polymerase itself. The result is a large, macromolecular machine that is positioned at a gene's start site and capable of starting transcription. Proteolytic enzymes being protein catabolism by breaking the peptide bonds of amino acids. Proteolytic enzymes could hydrolyze growth hormone but would not increase the production of growth hormone. The degradation of mRNA would decrease the cell's ability to produce growth hormone. The increased concentration of growth hormone in a cell would not increase the production of growth hormone.
Which of the following statements about the p53 protein is true? It activates genes that induce apoptosis in cells with extensively damaged DNA. It is a basal transcription factor that prevents initiation of transcription. It binds to damaged DNA and repairs it before allowing transcription to proceed. It ensures cell-cycle progression when DNA is damaged.
It activates genes that induce apoptosis in cells with extensively damaged DNA. * Activated p53 binds to the enhancers of genes that arrest the cell cycle, repair DNA damage, and when all else fails, trigger apoptosis (cell death).
Which of the following statements best describes a eukaryotic promoter? It is found upstream of the gene and contains the TATA box. It is found downstream of the gene and contains the TATA box. It is found upstream of the gene and is where sigma proteins bind. It is found downstream of the gene and is where sigma proteins bind.
It is found upstream of the gene and contains the TATA box. *The TATA box is generally located 25 base pairs upstream (not downstream) of the gene being transcribed.
Which of the following will decrease the rate of transcription? Repressors Basal transcription factors Activators Coactivators
Repressors
Which of the following statements is true about protein production in eukaryotes? Once mRNA is produced in the nucleus, the protein will always be produced. Splicing patterns in mRNA are critical to protein formation Once an RNA transcript is made, it is immediately transported out of the nucleus and a protein is formed. A single sequence of pre-mRNA always gives rise to the same protein.
Splicing patterns in mRNA are critical to protein formation *Because different cells use different splicing patterns, it is possible for different gene products (i.e., proteins) to result. During splicing, gene expression is regulated when selected exons are removed from the primary transcript along with the introns. When an RNA transcript is produced, alternative splicing, which is controlled by proteins that bind to RNAs in the nucleus, influence which sequences are used for splicing. Different cells use different splicing patterns. Therefore, a single sequence of pre-mRNA can give rise to different proteins depending on the splicing pattern.
Which of the following molecules is a basal transcription factor? TATA-binding protein (TBP) Mediator Histone acetyl transferase (HAT) RNA polymerase II
TATA-binding protein (TBP) * A large complex of proteins called mediator acts as a bridge between regulatory transcription factors, basal transcription factors, and RNA polymerase II. Histone acetyltransferases (HATs) add acetyl groups to the positively charged lysine residues in histones. RNA polymerase II catalyzes the transcription of DNA.
If cells carrying a mutant form of p53 that cannot activate transcription are exposed to UV radiation, what is the most likely immediate outcome? Progression through the cell cycle will halt until DNA damage is repaired. The cells will fail to repair DNA damage prior to the next cell division. Cells will activate cell-death (apoptosis) pathways. The cells immediately invade neighboring cells, leading to the formation of secondary tumors.
The cells will fail to repair DNA damage prior to the next cell division. *Researchers began to understand what p53 does when they exposed normal, noncancerous human cells to UV radiation and noticed that levels of active p53 protein increased markedly. UV radiation damages DNA. Follow-up studies confirmed that there is a close correlation between DNA damage and the amount of p53 in a cell. Activated p53 binds to the enhancers of genes that arrest the cell cycle and, if possible, repairs DNA damage. Activated p53 binds to the enhancers of genes and, if damage cannot be repaired, will trigger apoptosis (cell death). Mutant p53 will not invade neighboring cells but can halt the cell cycle or trigger apoptosis.
Which of the following experiments best supports the idea that a transcriptional regulatory sequence can be located in an intron of a gene? The intron of a gene is deleted, the gene is introduced into mouse cells, and the mRNA levels are measured. These mRNA levels are compared to a normal gene that is also introduced into mouse cells. The mutated gene shows no mRNA transcription, whereas the normal one does. The intron of a gene is deleted, the gene is introduced into mouse cells, and the mRNA levels are measured showing no mRNA expression. The gene containing all introns intact is introduced into mouse cells and the mRNA levels are measured. The mRNA is transcribed at high levels. The exon of a gene is deleted, the gene is introduced into mouse cells, and the mRNA levels are measured. These mRNA levels are compared to a normal gene that is also introduced into mouse cells. The mutated gene shows no mRNA transcription whereas the normal one does.
The intron of a gene is deleted, the gene is introduced into mouse cells, and the mRNA levels are measured. These mRNA levels are compared to a normal gene that is also introduced into mouse cells. The mutated gene shows no mRNA transcription, whereas the normal one does. *To process mRNA from a primary RNA transcript the introns have to be spliced out of primary transcripts. The mRNA is produced from the gene that has been introduced into the mouse cell. If the intron is removed from the gene and there is no mRNA transcription than the transcriptional regulatory sequences are located in the intron. However, to fully demonstrate that the sequences are located in the intron the control group (i.e., the normal cells) would have to be compared with the experimental group (the mutated cells). In this case, there is no comparison of the normal cells (the control group) and the mutated cells (the experimental group). To demonstrate that the transcriptional regulatory sequences are located in the intron, both groups are required for comparison. If the cells contain genes with the introns and the mRNA transcripts are produced at high levels then the introns could be the site of the transcriptional regulatory sequence. However, the lack of the experimental group does not exclude other possibilities. Exons are transcribed regions that are included in the mature RNA once splicing is complete. If the exons are removed (rather than the introns) the experiment is not examining the prediction that transcriptional regulatory sequences are located in the introns.
In smooth and striated muscle cells, the DNA for tropomyosin is the same, yet the mRNAs produced are different. Which of the following statements explains this phenomenon? The tropomyosin gene is very large and contains a large number of introns and exons. Distinct tropomyosin proteins are produced in the two cell types. A shorter region of the tropomyosin DNA in striated muscles cells is transcribed into mRNA, resulting in a smaller mRNA transcript. The presence of cell-type-specific molecules influences the splicing patterns of the mRNA.
The presence of cell-type-specific molecules influences the splicing patterns of the mRNA. *Alternative splicing is controlled by proteins that bind to RNAs in the nucleus and interact with spliceosomes to influence which sequences are used for splicing. When cells that are destined to become skeletal muscle or smooth muscle are developing, they receive signals leading to the production of specific proteins that are active in the regulation of splicing. Instead of transcribing different tropomyosin genes, the cells transcribe a single gene and splice the same primary RNA transcript in different ways. The primary transcript from the tropomyosin gene contains 14 exons. In each type of muscle cell, a different subset of the 14 exons are spliced together to produce two different mRNAs (see figure). As a result of alternative splicing, the tropomyosin proteins found in these two cell types are distinct. (However, this fact does not explain why the mRNAs are different.)
Which of the following statements about eukaryotic regulatory sequences is true? All increase transcription. They have the same activity or function in different cell types. They can function if their 5' to 3' orientation is reversed. All suppress transcription.
They can function if their 5' to 3' orientation is reversed. *Enhancers can work even if their normal 5′ 3′ orientation is flipped, or if they are moved to a new location in the vicinity of the gene.
How do histone deacetylases impact chromatin structure? They acetylate histones, making them more positively charged and condenses the chromatin. They acetylate histones, making them more negatively charged and condenses the chromatin. They deacetylate histones, making them more positively charged and condenses the chromatin. They deacetylate histones, making them more negatively charged, which decondenses the chromatin.
They deacetylate histones, making them more positively charged and condenses the chromatin. *Histone deacetylases (HDACs) remove acetyl groups from the positively charged lysine residues in histones. When HDACs remove acetyl groups from histones, this process usually leads to condensed chromatin that is more positively charged and condensed.
Which statement correctly explains one factor that contributes to the phenotypic difference between muscle cells and brain cells? Histone acetyl transferases affect chromatin structure only in brain cells. Histone deacetylases affect chromatin structure only in brain cells. They inherited different types of modified histones from their parental cells. Methyl groups are added to histones only in muscle cells.
They inherited different types of modified histones from their parental cells. *The pattern of chromatin modifications varies from one cell type to another. For example, suppose within an individual you analyzed the same gene in a muscle cell and a brain cell. This and other genes would likely have a different pattern of DNA methylation and histone acetylation in the two cell types. DNA methylation and histone modifications are an example of epigenetic inheritance, the collective term for patterns of inheritance that are due to something other than differences in DNA sequences. With epigenetic inheritance, if a cell received a "become muscle" signal early in development, it would modify its chromatin in distinctive ways and pass those modifications on to its descendants. Muscle cells are different from brain cells not because they contain different genes, but largely because they have inherited different patterns of DNA methylation and histone modifications during the course of their development. Histone acetyl transferases can affect chromatin structure in any cell in which DNA is present. Histone deacetylases can affect chromatin structure in any cell in which DNA is present. Methyl groups can be added to histones in any cell in which DNA is present.
Which eukaryotic protein binds to the promoter-proximal region of only some genes? The TATA box Sigma factor Transcriptional activators Enhancers
Transcriptional activators *Enhancers are regulatory DNA sequences unique to eukaryotes. When regulatory proteins called transcriptional activators bind to enhancers, transcription begins. Thus, enhancers and activators are like a gas pedal—an element in positive control. What is known is that promoters in eukaryotes are more complex than bacterial promoters, often containing two or three conserved sequences that serve as binding sites for proteins needed to start transcription. The most intensively studied of these is a sequence known as the TATA box. Once a promoter that contains a TATA box has been exposed by chromatin remodeling, the first step in initiating transcription is binding of the TATA-binding protein (TBP). Proteins related to TBP also work on promoters with other conserved sequences. But the binding of TBP or any of its relatives does not guarantee that a gene will be transcribed. In eukaryotes, a wide array of other DNA sequences and proteins work together to allow transcription. Sigma factors interact with promoters. Eukaryotes also possess regulatory sequences that are similar in structure and share key characteristics with enhancers but work to inhibit transcription. These DNA sequences are called silencers. When regulatory proteins called repressors bind to silencers, transcription is shut down. Silencers and repressors are like a brake—an element in negative control.
Which of the following statements is true of proto-oncogenes? When mutated, they become tumor suppressors, driving the cell cycle forward and promoting cancer. When mutated, they become oncogenes, driving the cell cycle forward and promoting cancer. When mutated, proto-oncogenes become oncogenes, alleles that inhibit cancer by halting the cell cycle. When mutated, they become tumor suppressors, halting cell-cycle progression until the signals are right to move forward.
When mutated, they become oncogenes, driving the cell cycle forward and promoting cancer. *Genes that stimulate cell division are called proto-oncogenes (literally, "first cancer genes"). In normal cells, the proteins produced from proto-oncogenes are active only when conditions are appropriate for growth. In cancerous cells, defects in the regulation of proto-oncogenes can cause these genes to stimulate growth at all times. (In the context of cancer, cell growth refers to an increase in cell numbers, not an increase in the size of individual cells.) In such cases, a mutation has converted the proto-oncogene into an oncogene—an allele that promotes cancer development. Proteins that stop or slow the cell cycle when conditions are unfavorable for cell division are called tumor suppressors. Logically enough, the genes that code for these proteins are called tumor suppressor genes. If the function of a tumor suppressor gene is lost because of mutation, then a key brake on the cell cycle is eliminated.
An enhancer is __________. always located upstream of the gene a region of DNA that may be located more than 100,000 bases away a protein that binds to the promoter, interacts with RNA polymerase, and helps to initiate transcription always located downstream of the gene
a region of DNA that may be located more than 100,000 bases away Regulatory sequences that are far from the promoter and activate transcription are termed enhancers. An enhancer can be located either upstream or downstream of the gene it is regulating. Transcription factors are proteins that bind to the promoter to assist in the initiation of transcription.
The life span of an mRNA molecule can be controlled by the activities of __________. the TATA-binding protein the RISC protein complex RNA polymerase regulatory transcription factors
the RISC protein complex *If the match between an mRNA and an mRNA is perfect, an enzyme in the RISC destroys the mRNA by cutting it in two. In effect, tight binding by an mRNA is a "kiss of death" for the mRNA. Once a promoter that contains a TATA box has been exposed by chromatin remodeling, the first step in initiating transcription is binding of the TATA-binding protein (TBP). Proteins related to TBP also work on promoters with other conserved sequences. But the binding of TBP or any of its relatives does not guarantee that a gene will be transcribed. RNA polymerase initiates transcription. Regulatory transcription factors you've learned about bind to enhancers, silencers, and promoter-proximal elements.