- 17.1 Summary of regulation of gene expression
- 17.2 Regulation of prokaryotic genes
- 17.3 Regulation of eukaryotic genes
Every somatic cell in the body usually contains the same DNA. (Some exceptions include red blood cells, which contain no DNA in their mature state, and some immune system cells that rearrange their DNA while making antibodies.) In general, the genes that determine whether you have green eyes or brown hair, or how fast you metabolize food are the same in eye cells as in liver cells, although these organs function quite differently. If all cells have the same DNA, how do cells differ in their structure and function? Why do eye cells differ so much from liver cells?
Although every cell in your body contains the same DNA sequences, not all cells activate or express the same set of genes. In fact, only a small subset of proteins is produced by any given cell. In other words, in any given cell, not all genes encoded in DNA are transcribed into mRNA or translated into proteins. Eye cells make a certain subset of proteins, and liver cells make a different subset of proteins. Also, at different times, liver cells can produce different subsets of liver proteins. The expression of specific genes is a highly regulated process with many levels and steps of control. This complexity ensures that each protein is expressed in the right cells at the right time.
By the end of this section, you will be able to:
- Discuss why each cell does not express all of its genes.
- Describe some of the major differences between prokaryotic and eukaryotic gene regulation.
For a cell to function properly, the necessary proteins must be synthesized at the right time. All cells control or regulate protein synthesis from the information encoded in their DNA. The process of "turning on" a gene to produce mRNA and protein is calledgene expression. Whether in a simple single-celled organism or a complex multicellular organism, each cell controls when its genes are expressed, how much protein is produced, and when it is time to stop producing that protein because it is no longer needed.
Regulation of gene expression conserves energy and space. It is more energy efficient to activate genes only when they are needed. Furthermore, expressing only a subset of genes in each cell saves space because the DNA must be uncoiled from its tightly coiled structure to transcribe and translate the DNA. Cells would have to be huge if all proteins were expressed in all cells all the time. Control of gene expression is extremely complex. Malfunctioning of this process is detrimental to the cell and can lead to the development of many diseases, including cancer.
17.1.1 Prokaryotic versus eukaryotic gene expression
Because prokaryotic organisms are single-celled organisms with no cell nucleus, their DNA floats freely in the cell's cytoplasm. When a particular protein is needed, the gene encoding it is transcribed into mRNA, which is simultaneously translated into protein. When the protein is no longer needed, transcription stops. As a result, the main method of controlling the amount of each protein that is expressed in a prokaryotic cell is the regulation of transcription.
Eukaryotic cells, by contrast, have intracellular organelles that add to their complexity. In eukaryotic cells, DNA is contained in the cell nucleus, where it is transcribed into mRNA. The newly synthesized mRNA is modified and transported out of the nucleus into the cytoplasm, where ribosomes translate the mRNA into protein. The transcription and translation processes are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation occurs only in the cytoplasm. Regulation of gene expression in eukaryotes can occur at all stages of the process (Figure 17.2).
Some of the differences in the regulation of gene expression between prokaryotes and eukaryotes are summarized inTabla 17.1.
Table 17.1 Differences in gene regulation of prokaryotes and eukaryotes.
DNA is found in the cytoplasm.
DNA is in the nucleus.
Transcription and translation occur almost simultaneously.
Transcription takes place in the nucleus before translation, which takes place in the cytoplasm.
Gene expression is mainly regulated at the transcriptional level.
Gene expression is regulated at several levels: epigenetic, transcriptional, nuclear transport, post-transcriptional, translational, and post-translational.
By the end of this section, you will be able to:
- Describe the steps involved in the regulation of prokaryotic genes.
- Explain the roles of activators, inducers, and repressors in gene regulation.
The DNA of prokaryotes is organized in a circular chromosome that resides in the cytoplasm of the cell. Proteins that are needed for a specific function, or that are involved in the same biochemical pathway, are often coded together in blocks calledoperones. For example, the five genes needed to produce the amino acid tryptophan in bacteriaE. coliare located next to each other in thejourneyoperon The genes in an operon are transcribed into a single mRNA molecule. This allows the genes to be controlled as a unit: all are expressed or none are expressed. Each operon needs only one regulatory region, including onedistrict attorney, where RNA polymerase binds, and aoperator, where other regulatory proteins bind.
In prokaryotic cells, there are three types of regulatory molecules that can affect the expression of operons.activatorsare proteins that increase the transcription of a gene.Represorasare proteins that suppress the transcription of a gene. Finally,inductorsare molecules that bind to repressors and inactivate them. Below are two examples of how these molecules regulate different operons.
17.2.1 Ojourneyoperon: a repressor operon
Like all cells, bacteria need amino acids to survive. Tryptophan is an amino acid that bacteriaE. colican ingest from the environment or synthesize. When E. coli needs to synthesize tryptophan, it must express a set of five proteins that are encoded by five genes. These five genes are located next to each other in thetryptophan (journey) operon(Figure 17.3).
When tryptophan is present in the environment,E. coliit is not necessary to synthesize it, and thejourneythe operon is off. However, when tryptophan availability is low, thejourneythe operon is activated so that genes are transcribed, proteins are produced, and tryptophan can be synthesized.
A DNA sequence called an operator is located between the promoter and the primer.journeygene. The operator contains the DNA code to which the repressor protein can bind. The repressor protein is regulated by tryptophan levels in the cell.
When tryptophan is present in the cell, two tryptophan molecules bind to thejourneyrepressor This causes the repressor to change shape and bind to thejourneyoperator. Binding of the tryptophan-repressor complex to the operator physically blocks RNA polymerase binding and transcription of downstream genes. So when the cell has enough tryptophan, you are preventing it from making more.
When tryptophan is not present in the cell, the repressor does not have tryptophan to bind to it. The repressor is not activated and does not bind to the operator. Therefore, RNA polymerase can transcribe the operon and produce the enzymes to synthesize tryptophan. So when the cell doesn't have enough tryptophan, it synthesizes it.
17.2.2 Otired outOperon: an inducing operon
Otired outoperate onE. coliit has a more complex regulation, involving a repressor and an activator.MI. coliuses glucose for food, but can use other sugars, such as lactose, when glucose concentrations are low. Three proteins are needed to break down lactose; are encoded by the three genes of thetired outoperon
When lactose is not present, protein is not needed to digest lactose. Therefore, a repressor binds to the operator and prevents the operon from being transcribed by RNA polymerase.
When lactose is present, the lactose binds to the repressor and removes it from the operator. RNA polymerase is now free to transcribe the genes needed to digest lactose (Figure 17.4)
However, the story is more complex than that. FromE. coliprefers to use glucose as food, thetired outThe operon is only expressed at low levels even when the repressor is removed. But what happens when ONLY lactose is present? Now the bacteria need to increase the production of proteins that digest lactose. It does this by using an activating protein called catabolite activating protein (CAP).
When glucose levels drop, cyclic AMP (cAMP) begins to accumulate in the cell. cAMP binds to CAP and the complex binds totired outoperon promoter (Figure 17.5). This increases the ability of the RNA polymerase to bind to the promoter and increases gene transcription.
In short, for thetired outFor the operon to be fully activated, two conditions must be met. First, the glucose level must be very low or non-existent. Second, lactose must be present. Only when glucose is absent and lactose is present, thetired outthe operon is maximally transcribed. This makes sense for the cell, because it would be a waste of energy to create the proteins to process lactose if glucose were abundant or lactose was not available (Tabla 17.2).
Table 17.2 Summary of signals that induce or repress the transcription of thetired outoperon
By the end of this section, you will be able to:
- Explain the process of epigenetic gene regulation in eukaryotic cells.
- Explain the process of regulation of transcriptional genes in eukaryotic cells.
- Explain the process of post-transcriptional gene regulation in eukaryotic cells.
- Explain the process of regulation of translational genes in eukaryotic cells.
- Explain the process of post-transcriptional gene regulation in eukaryotic cells.
In eukaryotes, the control of gene expression is more complex and can occur at many different levels. Eukaryotic genes are not organized into operons, so each gene must be regulated independently. Also, eukaryotic cells have many more genes than prokaryotic cells. Regulation of gene expression can occur at any stage, as DNA is transcribed into mRNA and mRNA is translated into protein. For convenience, regulation is divided into five levels: epigenetic, transcriptional, posttranscriptional, translational, and posttranslational.Figure 17.6).
The first level of control of gene expression isepigenetic(“about genetics”). Epigenetics is a relatively new but growing field of biology.
Epigenetic control involves changes to genes that do not alter the nucleotide sequence of DNA and are not permanent. Rather, these changes modify the chromosome structure so that genes can be turned on or off. This level of control occurs through inherited chemical modifications of DNA and/or chromosomal proteins.
An example of chemical modification of DNA is the addition of methyl groups to DNA in a process called methylation. In general, methylation suppresses transcription. Interestingly, methylation patterns can be passed on as cells divide. Therefore, parents can pass on the tendency for a gene to be expressed in their offspring. Other inherited chemical modifications of DNA can also occur.
Modification of histone proteins is an example of epigenetic control
The best-studied example of epigenetic regulation is the modification of histone proteins. Histones are chromosomal proteins that tightly coil DNA to fit into a cell's nucleus. The human genome, for example, consists of more than three billion pairs of nucleotides. An average chromosome contains 130 million nucleotide pairs, and each cell in the body contains 46 chromosomes. If stretched linearly, an average human chromosome would be more than four centimeters long. To fit all that DNA into the nucleus of a microscopic cell, the DNA must be tightly coiled around proteins. It is also arranged so that specific segments can be accessed as needed for a specific cell type (Figure 17.7).
The first level of organization, or packaging, is the coiling of DNA strands around histone proteins. Histones package and arrange DNA into structural units called nucleosome complexes, which can control protein access to regions of DNA.Figure 17.8a). Under the electron microscope, this winding of DNA around histone proteins to form nucleosomes looks like little beads on a string (Figure 17.8b). These spheres (histone proteins) can move along the strand (DNA) and change the structure of the molecule.
If a gene is transcribed, the nucleosomes surrounding that region of DNA can slide across the DNA to open up that particular chromosomal region and allow access for RNA polymerase and other proteins, called transcription factors, to bind to the promoter region and start transcription. If a gene remains turned off or silenced, the histone proteins and DNA will undergo different modifications that signal a closed chromosome configuration. In this closed configuration, RNA polymerase and transcription factors do not have access to the DNA and transcription cannot take place.Figure 17.9).
The way the histones move depends on the signals found on the histones. These signals are "tags," in the form of phosphate, methyl, or acetyl groups, that open or close a chromosomal region (Figure 17.9). These tags are not permanent, but can be added or removed as needed. Since DNA is negatively charged, changes in the charge on the histones will change the degree of folding of the DNA molecule. When unmodified, histone proteins have a large positive charge; by adding chemical modifications like acetyl groups, the charge becomes less positive.
17.3.2 Transcription control of gene expression
transcriptional regulationit is the control of whether or not an mRNA is transcribed from a gene in a particular cell. Like prokaryotic cells, gene transcription in eukaryotes requires RNA polymerase to bind to a promoter to initiate transcription. In eukaryotes, RNA polymerase requires other proteins, ortranscription factors, to facilitate initiation of transcription. Transcription factors are proteins that bind to the promoter sequence and other regulatory sequences to control the transcription of the target gene. RNA polymerase alone cannot initiate transcription in eukaryotic cells. Transcription factors must first bind to the promoter region and recruit RNA polymerase to the transcription initiation site.
The promoter and transcription factors
In eukaryotic genes, the promoter region is located immediately upstream of the coding sequence. This region can vary from a few to hundreds of nucleotides in length. Promoter length is gene-specific and can differ drastically between genes. The longer the promoter, the more space available for proteins to bind to. Consequently, the level of control of gene expression can differ drastically between genes. The purpose of the promoter is to activate transcription factors that control the initiation of transcription.Figure 17.10, topo).
Within the promoter region, just above the transcription start site, resides the TATA box. This box is simply a thymine adenine dinucleotide repeat (literally, TATA repeats). The transcription factors bind to the TATA box and form an initiation complex. Once this complex is assembled, RNA polymerase binds to its previous sequence and becomes phosphorylated. This releases some of the protein from the DNA, activates the transcription initiation complex, and puts the RNA polymerase in the correct orientation to begin transcription (Figure 17.10, topo).
Enhancers and Repressors
In some eukaryotic genes, there are regions that help increase transcription. These regions, calledintensifiers, are not necessarily close to genes; they can be located thousands of nucleotides away. They can be found upstream, within the coding region, or downstream of a gene. Enhancers are binding sites for activators. When an enhancer is far from a gene, the DNA folds in such a way that the enhancer moves closer to the promoter, allowing interaction between the activators and the transcription initiation complex.Figure 17.10, lower).
Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptionrepresorasit can bind to promoter or enhancer regions and block transcription. Both activators and repressors respond to external stimuli to determine which genes should be expressed.
17.3.3 Post-transcriptional control of gene expression
Post-transcriptional regulationit occurs after the mRNA is transcribed but before translation begins. This regulation can occur at the level of mRNA processing, transport from the nucleus to the cytoplasm, or binding to ribosomes.
alternative RNA splicing
Recall from Chapter 5 that in eukaryotic cells, the primary RNA transcript usually contains introns, which are removed prior to translation.
alternative RNA splicingit is a mechanism that allows different combinations of introns, and sometimes exons, to be removed from the primary transcript.Figure 17.11). This allows different protein products to be produced from one gene. Alternative splicing may act as a gene regulation mechanism. Differential splicing is used to produce different protein products in different cells or at different times within the same cell. Alternative splicing is now understood to be a common mechanism of gene regulation in eukaryotes; up to 70% of genes in humans are expressed as multiple proteins through alternative splicing.
Alternative splicing evolution
How might alternative splicing evolve? Introns have an initial and final recognition sequence; it is easy to imagine that the splicing mechanism fails to identify the end of one intron and instead finds the end of the next intron, thus removing two introns and the intervening exon. In fact, there are mechanisms to prevent such intron skipping, but mutations are likely to lead to their failure. Such "mistakes" would likely produce a non-functional protein. In fact, the cause of many genetic diseases is alternative splicing rather than mutations in a sequence. However, alternative splicing would create a protein variant without losing the original protein, opening up possibilities to adapt the new variant to new functions. Gene duplication has played an important role in the evolution of new functions in a similar way, providing genes that can be evolved without deleting the original functional protein.
RNA stability check
Another type of post-transcriptional control involves the stability of mRNA in the cytoplasm. The longer an mRNA exists in the cytoplasm, the longer it has to be translated and the more protein is produced. Many factors contribute to the stability of the mRNA, including the length of its poly-A tail.
The proteins, called RNA-binding proteins (RBPs), can bind to regions of RNA immediately upstream or downstream of the protein-coding region. Regions of RNA that are not translated into proteins are calleduntranslated regionsor UTR. The region just before the coding region of the protein is called5'UTR, while the region after the coding region is called3'UTR(Figure17.12). Binding of RBPs to these regions can either increase or decrease the stability of an RNA molecule, depending on the specific RBP being bound.
microARN, omiARN, it can also bind to the RNA molecule. miRNAs are short RNA molecules (21–24 nucleotides) that are produced in the nucleus as longer pre-miRNAs and then cleaved into mature miRNAs by a protein calleddice game. miRNAs bind to mRNA along with a ribonucleoprotein complex calledRNA-induced silencing complex (RISC).The RISC-miRNA complex rapidly degrades the target mRNA.
17.3.4 Translational control of gene expression
Once an mRNA has been transported to the cytoplasm, it is translated into proteins. The control of this process is highly dependent on the mRNA molecule. As discussed above, the stability of the mRNA will have a large impact on its translation into a protein. Translation can also be regulated at the level of mRNA binding to the ribosome. Once the mRNA binds to the ribosome, the rate and level of translation can still be controlled. An example of translational control occurs in proteins destined to end up in an organelle called the endoplasmic reticulum (ER). The first amino acids in these proteins are a tag called a signal sequence. Once these amino acids are translated, a signal recognition particle (SRP) binds to the signal sequence and arrests translation while the mRNA-ribosome complex is transported to the ER. Once they arrive, the SRP is removed and translation resumes.
17.3.5 Posttranslational control of gene expression
The ultimate level of control of gene expression in eukaryotes ispost-translational regulation. This type of control involves modifying the protein after it is produced to affect its activity. An example of post-translational regulation is enzyme inhibition. When an enzyme is no longer needed, it is inhibited by a competitive or allosteric inhibitor, preventing it from binding to its substrate. The inhibition is reversible, so the enzyme can be reactivated later. This is more efficient than breaking down the enzyme when it's not needed and making more of it when it's needed again.
The activity and/or stability of proteins can also be regulated by the addition of functional groups, such as methyl, phosphate or acetyl groups. Sometimes these modifications can regulate where a protein is found in the cell, for example, in the nucleus, the cytoplasm, or attached to the plasma membrane.
adding aubiquitinagroup to a protein marks that protein for degradation. Ubiquitin acts as a flag indicating that the protein's lifespan is complete. The tagged proteins move to aproteasoma, an organelle that breaks down proteins (Figure 17.13). Therefore, one way to control gene expression is to alter the longevity of proteins.
What is regulation of gene expression chapter 17? ›
The regulation of gene expression conserves energy and space. It is more energy efficient to turn on the genes only when they are required. In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly coiled structure to transcribe and translate the DNA.What is gene expression quizlet Chapter 17? ›
What is gene expression? The process by which DNA directs the synthesis of proteins (or sometimes just RNA's).What is the regulation of gene expression explain? ›
Regulation of Gene Expression
This process is a tightly coordinated process which allows a cell to respond to its changing environment. During gene expression, genetic codes from the DNA code are converted into a protein with the help of translation and transcription.
Definition. Gene expression is the process by which the information encoded in a gene is turned into a function. This mostly occurs via the transcription of RNA molecules that code for proteins or non-coding RNA molecules that serve other functions.What are the 3 elements of gene expression? ›
Regulation of transcription can be broken down into three main routes of influence; genetic (direct interaction of a control factor with the gene), modulation interaction of a control factor with the transcription machinery and epigenetic (non-sequence changes in DNA structure that influence transcription).What are the 4 mechanisms of gene regulation? ›
regulation of gene expression by proteins binding to DNA regulatory elements. alternative mRNA splicing. regulation of gene expression through chromatin accessibility.What is gene expression PDF? ›
Gene expression is the process by which. information from a gene is used in the synthesis of. a functional gene product. These products are often. proteins, but in non-protein coding genes such as.What is gene expression short answer? ›
The process by which a gene gets turned on in a cell to make RNA and proteins. Gene expression may be measured by looking at the RNA, or the protein made from the RNA, or what the protein does in a cell.What is gene expression answers? ›
Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein.Why is gene expression regulation important? ›
The regulation of gene expression conserves energy and space. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required.
What controls regulation of gene expression? ›
Gene expression is primarily controlled at the level of transcription, largely as a result of binding of proteins to specific sites on DNA.Why is gene expression important? ›
Gene expression is important because a specific protein can be produced only when its gene is turned on. But it takes more than one step to get from gene to protein, and the process of building proteins is a key step in the gene expression pathway that can be altered in cancer.What is gene regulation quizlet? ›
Gene Regulation. Refers to the ability of cells to control the expression of their genes. Cell Differentation. The process by which cells become specialized into particular types.Why is regulation of gene expression important quizlet? ›
We regulate gene expression because transcription and translation take lots of energy so we need it. And it would be a waste of energy to make all proteins in all cells.