16: Gene Expression Flashcards
Regulation of Gene Expression, Prokaryotic Gene Regulation, Eukaryotic Epigenetic Gene Regulation, Eukaryotic Transcription Gene Regulation, Eukaryotic Post-transcriptional Gene Regulation, Eukaryotic Translational and Post-translational Gene Regulation, Cancer and Gene Regulation (86 cards)
1
Q
What does it mean to be epigenetic?
A
Heritable changes that do not involve changes in the DNA sequence.
2
Q
What is gene expression?
A
Processes that control the turning on or turning off of a gene.
3
Q
What is post-transcriptional gene expression?
A
Control of gene expression after the RNA molecule has been created by before it is translated into a protein.
4
Q
What is post-translational gene expression?
A
Control of gene expression after a protein has been created.
5
Q
Where is gene expression regulated in prokaryotes?
A
In prokaryotes, to synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the resulting protein is no longer needed, transcription stops. As a result, the primary method to control what type of protein and how much of each protein is expressed in a prokaryotic cell is the regulation of DNA transcription. All of the subsequent steps occur automatically. When more protein is required, more transcription occurs. Therefore, in prokaryotic cells, the control of gene expression is mostly at the transcriptional level.
6
Q
Where is gene expression regulated in eukaryotes?
A
Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level), when the RNA is translated into protein (translational level), or after the protein has been made (post-translational level).
7
Q
How did gene regulation evolve?
A
Some cellular processes arose from the need of the organism to defend itself. Cellular processes such as gene silencing developed to protect the cell from viral or parasitic infections. If the cell could quickly shut off gene expression for a short period of time, it would be able to survive an infection when other organisms could not. Therefore, the organism evolved a new process that helped it survive, and it was able to pass this new development to offspring.
8
Q
What is an activator?
A
A protein that binds to prokaryotic operators to increase transcription.
9
Q
What is a catabolite activator protein (CAP)?
A
A protein that complexes with cAMP to bind to the promoter sequences of operons that control sugar processing when glucose is not available.
10
Q
What is an inducer?
A
A small molecule that either activates or represses transcription depending on the needs of the cell and the availability of substrate.
11
Q
What is an inducible operon?
A
An operon that can be activated or repressed depending on cellular needs and the surrounding environment.
12
Q
What is a lac operon?
A
An operon in prokaryotic cells that encodes genes required for processing and intake of lactose.
13
Q
What is a negative regulator?
A
A protein that prevents transcription.
14
Q
What is an operator?
A
A region of DNA outside of the promoter region that binds activators or repressors that control gene expression in prokaryotic cells.
15
Q
What is an operon?
A
Collection of genes involved in a pathway that are transcribed together as a single mRNA in prokaryotic cells.
16
Q
What is a positive regulator?
A
A protein that increases transcription.
17
Q
What is a repressor?
A
A protein that binds to the operator of prokaryotic genes to prevent transcription.
18
Q
What is the transcriptional start site?
A
The site at which transcription begins.
19
Q
What is a trp operon?
A
A series of genes necessary to synthesize tryptophan in prokaryotic cells.
20
Q
What is tryptophan?
A
An amino acid that can be synthesized by prokaryotic cells when necessary.
21
Q
What are the types of regulatory molecules in prokaryotic cells?
A
There are three types of regulatory molecules that can affect the expression of operons: repressors, activators, and inducers.
22
Q
What are some examples of repressors, activators, and inducers?
A
The trp operon is a repressor, catabolite activator protein (CAP) is an activator, and the lac operon is an inducer.
23
Q
What happens to the trp operator in the presence of tryptophan?
A
A DNA sequence called the operator sequence is encoded between the promoter region and the first trp coding gene. This operator contains the DNA code to which the repressor protein can bind. When tryptophan is present in the cell, two tryptophan molecules bind to the trp repressor, which changes shape to bind to the trp operator. Binding of the tryptophan–repressor complex at the operator physically prevents the RNA polymerase from binding, and transcribing the downstream genes.
24
Q
Is the trp operon positively or negatively regulated?
A
When tryptophan is not present in the cell, the repressor by itself does not bind to the operator; therefore, the operon is active and tryptophan is synthesized. Because the repressor protein actively binds to the operator to keep the genes turned off, the trp operon is negatively regulated and the proteins that bind to the operator to silence trp expression are negative regulators.
25
What is an example of positive regulation in prokaryotes?
When glucose is scarce, E. coli bacteria can turn to other sugar sources for fuel. To do this, new genes to process these alternate genes must be transcribed. When glucose levels drop, cyclic AMP (cAMP) begins to accumulate in the cell. The cAMP molecule is a signaling molecule that is involved in glucose and energy metabolism in E. coli. When glucose levels decline in the cell, accumulating cAMP binds to the positive regulator catabolite activator protein (CAP), a protein that binds to the promoters of operons that control the processing of alternative sugars. When cAMP binds to CAP, the complex binds to the promoter region of the genes that are needed to use the alternate sugar sources. In these operons, a CAP binding site is located upstream of the RNA polymerase binding site in the promoter. This increases the binding ability of RNA polymerase to the promoter region and the transcription of the genes.
26
How does the lac operon work?
E. coli is able to use other sugars as energy sources when glucose concentrations are low. To do so, the cAMP–CAP protein complex serves as a positive regulator to induce transcription. One such sugar source is lactose. The lac operon encodes the genes necessary to acquire and process the lactose from the local environment. CAP binds to the operator sequence upstream of the promoter that initiates transcription of the lac operon. However, for the lac operon to be activated, two conditions must be met. First, the level of glucose must be very low or non-existent. Second, lactose must be present. Only when glucose is absent and lactose is present will the lac operon be transcribed. This makes sense for the cell, because it would be energetically wasteful to create the proteins to process lactose if glucose was plentiful or lactose was not available.
27
What is a transcription factor?
A protein that binds to the DNA at the promoter or enhancer region and that influences transcription of a gene.
28
What happens to nucleosomes when their DNA must be transcribed?
If DNA encoding a specific gene is to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down the DNA to open that specific chromosomal region and allow for the transcriptional machinery (RNA polymerase) to initiate transcription. Nucleosomes can move to open the chromosome structure to expose a segment of DNA, but do so in a very controlled manner.
29
How can signals be used for epigenetic regulation in eukaryotes?
How the histone proteins move is dependent on signals found on both the histone proteins and on the DNA. These signals are tags added to histone proteins and DNA that tell the histones if a chromosomal region should be open or closed. These tags are not permanent, but may be added or removed as needed. They are chemical modifications (phosphate, methyl, or acetyl groups) that are attached to specific amino acids in the protein or to the nucleotides of the DNA. The tags do not alter the DNA base sequence, but they do alter how tightly wound the DNA is around the histone proteins. DNA is a negatively charged molecule; therefore, changes in the charge of the histone will change how tightly wound the DNA molecule will be. When unmodified, the histone proteins have a large positive charge; by adding chemical modifications like acetyl groups, the charge becomes less positive.
30
How can CpG islands be used for epigenetic regulation in eukaryotes?
The DNA molecule itself can also be modified. This occurs within very specific regions called CpG islands. These are stretches with a high frequency of cytosine and guanine dinucleotide DNA pairs (CG) found in the promoter regions of genes. When this configuration exists, the cytosine member of the pair can be methylated (a methyl group is added). This modification changes how the DNA interacts with proteins, including the histone proteins that control access to the region. Highly methylated (hypermethylated) DNA regions with deacetylated histones are tightly coiled and transcriptionally inactive.
31
What is a cis-acting element?
A transcription factor binding sites within the promoter that regulate the transcription of a gene adjacent to it.
32
What is an enhancer?
A segment of DNA that is upstream, downstream, perhaps thousands of nucleotides away, or on another chromosome that influence the transcription of a specific gene.
33
What is a trans-acting element?
A transcription factor binding site found outside the promoter or on another chromosome that influences the transcription of a particular gene.
34
What is a transcription factor binding site?
A sequence of DNA to which a transcription factor binds.
35
Where is the promoter located and how long is it?
The promoter region is immediately upstream of the coding sequence. This region can be short (only a few nucleotides in length) or quite long (hundreds of nucleotides long). The longer the promoter, the more available space for proteins to bind. This also adds more control to the transcription process. The length of the promoter is gene-specific and can differ dramatically between genes. Consequently, the level of control of gene expression can also differ quite dramatically between genes. The purpose of the promoter is to bind transcription factors that control the initiation of transcription.
36
How is transcription initiated in eukaryotes?
Within the promoter region, just upstream of the transcriptional start site, resides the TATA box. This box is simply a repeat of thymine and adenine dinucleotides (literally, TATA repeats). RNA polymerase binds to the transcription initiation complex, allowing transcription to occur. To initiate transcription, a transcription factor (TFIID) is the first to bind to the TATA box. Binding of TFIID recruits other transcription factors, including TFIIB, TFIIE, TFIIF, and TFIIH to the TATA box. Once this complex is assembled, RNA polymerase can bind to its upstream sequence. When bound along with the transcription factors, RNA polymerase is phosphorylated. This releases part of the protein from the DNA to activate the transcription initiation complex and places RNA polymerase in the correct orientation to begin transcription; DNA-bending protein brings the enhancer, which can be quite a distance from the gene, in contact with transcription factors and mediator proteins.
37
How are enhancers used to regulate gene expression?
Enhancer regions are binding sequences, or sites, for transcription factors. When a DNA-bending protein binds, the shape of the DNA changes. This shape change allows for the interaction of the activators bound to the enhancers with the transcription factors bound to the promoter region and the RNA polymerase. Whereas DNA is generally depicted as a straight line in two dimensions, it is actually a three-dimensional object. Therefore, a nucleotide sequence thousands of nucleotides away can fold over and interact with a specific promoter.
An enhancer is a DNA sequence that promotes transcription. Each enhancer is made up of short DNA sequences called distal control elements. Activators bound to the distal control elements interact with mediator proteins and transcription factors. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.
38
How are non-general transcription factors used to regulate gene expression?
In addition to the general transcription factors, other transcription factors can bind to the promoter to regulate gene transcription. These transcription factors bind to the promoters of a specific set of genes. They are not general transcription factors that bind to every promoter complex, but are recruited to a specific sequence on the promoter of a specific gene. There are hundreds of transcription factors in a cell that each bind specifically to a particular DNA sequence motif. Transcription factors respond to environmental stimuli that cause the proteins to find their binding sites and initiate transcription of the gene that is needed.
39
How are repressors used to regulate gene expression?
Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli to prevent the binding of activating transcription factors.
40
What is 3' UTR?
3' untranslated region; region just downstream of the protein-coding region in an RNA molecule that is not translated.
41
What is 5' cap?
A methylated guanosine triphosphate (GTP) molecule that is attached to the 5' end of a messenger RNA to protect the end from degradation.
42
What is 5' UTR?
5' untranslated region; region just upstream of the protein-coding region in an RNA molecule that is not translated.
43
What is a dicer?
An enzyme that chops the pre-miRNA into the mature form of the miRNA.
44
What is microRNA (miRNA)?
A small RNA molecule (approximately 21-24 nucleotides in length) that binds to RNA molecules to degrade them.
45
What is a poly-A tail?
A series of adenine nucleotides that are attached to the 3' end of an mRNA to protect the end from degradation.
46
What is an RNA-binding protein (RBP)?
A protein that binds to the 3' or 5' UTR to increase or decrease the RNA stability.
47
What is RNA stability?
How long an RNA molecule will remain intact in the cytoplasm.
48
What is an untranslated region?
A segment of the RNA molecule that is not translated into protein. These regions lie upstream (5') or downstream (3') the protein-coding region.
49
What is RISC?
A protein complex that binds along with the miRNA to the RNA to degrade it.
50
What is alternative RNA splicing?
Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of introns, and sometimes exons, are removed from the transcript. This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is now understood to be a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing.
51
How did alternative RNA splicing evolve?
Splicing mechanisms could fail to identify the end sequence of an intron and instead find the end of the subsequent intron, removing the intervening exon. Though there are mechanisms in place to prevent intron skipping, mutations could lead to their failure. This would most likely produce a nonfunctional protein. Indeed, the cause of many genetic diseases is alternative splicing rather than mutations in a sequence. However, alternate splicing could create a protein variant without the loss of the original protein, allowing for adaptation of the new variant to new functions. Gene duplication has played an important role in the evolution of new functions in a similar way by providing genes that may evolve without eliminating the original, functional protein.
52
How can gene expression be regulated by control of RNA stability?
Once the RNA is transported to the cytoplasm, the length of time that the RNA resides there can be controlled. Each RNA molecule has a defined lifespan and decays at a specific rate. This rate of decay can influence how much protein is in the cell. If the decay rate is increased, the RNA will not exist in the cytoplasm as long, shortening the time for translation to occur. Conversely, if the rate of decay is decreased, the RNA molecule will reside in the cytoplasm longer and more protein can be translated. This rate of decay is referred to as the RNA stability. If the RNA is stable, it will be detected for longer periods of time in the cytoplasm.
53
What do untranslated regions do?
They are regions that regulate mRNA localization, stability, and protein translation.
54
How can RBPs be used to regulate gene expression?
RBPs, can bind to UTRs, which can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.
55
How can miRNA be used to regulate gene expression?
miRNAs are made in the nucleus as longer pre-miRNAs. These pre-miRNAs are chopped into mature miRNAs by a protein called dicer. Like transcription factors and RBPs, mature miRNAs recognize a specific sequence and bind to the RNA; however, miRNAs also associate with a ribonucleoprotein complex called the RNA-induced silencing complex (RISC). RISC binds along with the miRNA to degrade the target mRNA. Together, miRNAs and the RISC complex rapidly destroy the RNA molecule.
56
What is eukaryotic initiation factor-2 (eIF-2)?
A protein that binds first to an mRNA to initiate translation.
57
What is guanosine diphosphate (GDP)?
A molecule that is left after the energy is used to start translation.
58
What is guanosine triphosphate (GTP)?
An energy-providing molecule that binds to eIF-2 and is needed for translation.
59
What is an initiation complex?
A protein complex containing eIF-2 that starts translation.
60
What is the large 60S ribosomal subunit?
The second, larger ribosomal subunit that binds to the RNA to translate it into protein.
61
What is a proteasome?
An organelle that degrades proteins.
62
What is the small 40S ribosomal subunit?
A ribosomal subunit that binds to the RNA to translate it into protein.
63
How is translation initiated in eukaryotes?
In translation, the complex that assembles to start the process is referred to as the initiation complex. The first protein to bind to the RNA to initiate translation is the eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein is active when it binds to the high-energy molecule guanosine triphosphate (GTP). GTP provides the energy to start the reaction by giving up a phosphate and becoming guanosine diphosphate (GDP). The eIF-2 protein bound to GTP binds to the small 40S ribosomal subunit. When bound, the methionine initiator tRNA associates with the eIF-2/40S ribosome complex, bringing along with it the mRNA to be translated. At this point, when the initiator complex is assembled, the GTP is converted into GDP and energy is released. The phosphate and the eIF-2 protein are released from the complex and the large 60S ribosomal subunit binds to translate the RNA.
64
How can the initiation complex be used to regulate gene expression?
The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly and translation is impeded. When eIF-2 remains unphosphorylated, it binds the RNA and actively translates the protein.
65
How can chemical modification of proteins be used to regulate gene expression?
Proteins can be chemically modified with the addition of groups including methyl, phosphate, acetyl, and ubiquitin groups. The addition or removal of these groups from proteins regulates their activity or the length of time they exist in the cell. 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.
66
What are the causes and effects of chemical modifications of proteins on regulation of gene expression?
Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure. These changes can alter epigenetic accessibility, transcription, mRNA stability, or translation—all resulting in changes in expression of various genes. This is an efficient way for the cell to rapidly change the levels of specific proteins in response to the environment. Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter transcription (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).
67
How can gene expression be regulated by altering protein longevity?
The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein.
68
What is DNA methylation?
An epigenetic modification that leads to gene silencing; commonly found in cancer cells.
69
What is histone acetylation?
An epigenetic modification that leads to gene silencing; commonly found in cancer cells.
70
What is myc?
An oncogene that causes cancer in many cells.
71
What are the effects of mutations in cancer cells?
In cancer cells, mutations modify cell-cycle control and cells don’t stop growing as they normally would. Mutations can also alter the growth rate or the progression of the cell through the cell cycle.
72
What is an example of a mutation that causes cancer by increasing the cell growth rate?
One example of a gene modification that alters the growth rate is increased phosphorylation of cyclin B, a protein that controls the progression of a cell through the cell cycle and serves as a cell-cycle checkpoint protein. As a result, cells can progress through the cell cycle unimpeded, even if mutations exist in the cell and its growth should be terminated. This post-translational change of cyclin B prevents it from controlling the cell cycle and contributes to the development of cancer.
73
How can abnormalities in gene expression be used to detect cancer?
Changes in epigenetic regulation, transcription, RNA stability, protein translation, and post-translational control can be detected in cancer. While these changes don’t occur simultaneously in one cancer, changes at each of these levels can be detected when observing cancer at different sites in different individuals. Therefore, changes in histone acetylation (epigenetic modification that leads to gene silencing), activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification can all be detected at some point in various cancer cells.
74
How can mutations in tumor suppressor genes lead to cancer?
The most studied tumor suppressor gene is p53, which is mutated in over 50 percent of all cancer types. The p53 protein itself functions as a transcription factor. It can bind to sites in the promoters of genes to initiate transcription. Therefore, the mutation of p53 in cancer will dramatically alter the transcriptional activity of its target genes.
75
How can proto-oncogenes lead to cancer?
Proto-oncogenes are positive cell-cycle regulators. When mutated, proto-oncogenes can become oncogenes and cause cancer. Overexpression of the oncogene can lead to uncontrolled cell growth. This is because oncogenes can alter transcriptional activity, stability, or protein translation of another gene that directly or indirectly controls cell growth.
76
What is an example of a disease caused by an oncogene?
An example of an oncogene involved in cancer is a protein called myc. Myc is a transcription factor that is aberrantly activated in Burkett’s Lymphoma, a cancer of the lymph system. Overexpression of myc transforms normal B cells into cancerous cells that continue to grow uncontrollably. High B-cell numbers can result in tumors that can interfere with normal bodily function. Patients with Burkett’s lymphoma can develop tumors on their jaw or in their mouth that interfere with the ability to eat.
77
How can gene silencing in epigenetics lead to cancer?
Silencing genes through epigenetic mechanisms is also very common in cancer cells. There are characteristic modifications to histone proteins and DNA that are associated with silenced genes. In cancer cells, the DNA in the promoter region of silenced genes is methylated on cytosine DNA residues in CpG islands. Histone proteins that surround that region lack the acetylation modification that is present when the genes are expressed in normal cells. This combination of DNA methylation and histone deacetylation (epigenetic modifications that lead to gene silencing) is commonly found in cancer. When these modifications occur, the gene present in that chromosomal region is silenced. Because these changes are temporary and can be reversed—for example, by preventing the action of the histone deacetylase protein that removes acetyl groups, or by DNA methyl transferase enzymes that add methyl groups to cytosines in DNA—it is possible to design new drugs and new therapies to take advantage of the reversible nature of these processes. Indeed, many researchers are testing how a silenced gene can be switched back on in a cancer cell to help re-establish normal growth patterns.
78
How can mutations that affect transcription lead to cancer?
Mutations that activate transcription factors, such as increased phosphorylation, can increase the binding of a transcription factor to its binding site in a promoter. This could lead to increased transcriptional activation of that gene that results in modified cell growth. Alternatively, a mutation in the DNA of a promoter or enhancer region can increase the binding ability of a transcription factor. This could also lead to the increased transcription and aberrant gene expression that is seen in cancer cells.
79
What is an example of cancer caused by overactive transcription and how can it be treated?
In breast cancer, for example, many proteins are overexpressed. This can lead to increased phosphorylation of key transcription factors that increase transcription. One such example is the overexpression of the epidermal growth factor receptor (EGFR) in a subset of breast cancers. The EGFR pathway activates many protein kinases that, in turn, activate many transcription factors that control genes involved in cell growth. New drugs that prevent the activation of EGFR have been developed and are used to treat these cancers.
80
How can altered expression of miRNA lead to cancer?
Several groups of researchers have shown that specific cancers have altered expression of miRNAs. Because miRNAs bind to the 3' UTR of RNA molecules to degrade them, overexpression of these miRNAs could be detrimental to normal cellular activity. Too many miRNAs could dramatically decrease the RNA population leading to a decrease in protein expression. Several studies have demonstrated a change in the miRNA population in specific cancer types. It appears that the subset of miRNAs expressed in breast cancer cells is quite different from the subset expressed in lung cancer cells or even from normal breast cells. This suggests that alterations in miRNA activity can contribute to the growth of breast cancer cells. These types of studies also suggest that if some miRNAs are specifically expressed only in cancer cells, they could be potential drug targets. It would, therefore, be conceivable that new drugs that turn off miRNA expression in cancer could be an effective method to treat cancer.
81
What are some post-translational modifications of proteins that can lead to cancer?
Modifications are found in cancer cells from the increased translation of a protein to changes in protein phosphorylation to alternative splice variants of a protein.
82
What is an example of mistakes in protein expression that can lead to cancer?
An example of how the expression of an alternative form of a protein can have dramatically different outcomes is seen in colon cancer cells. The c-Flip protein, a protein involved in mediating the cell death pathway, comes in two forms: long (c-FLIPL) and short (c-FLIPS). Both forms appear to be involved in initiating controlled cell death mechanisms in normal cells. However, in colon cancer cells, expression of the long form results in increased cell growth instead of cell death. Clearly, the expression of the wrong protein dramatically alters cell function and contributes to the development of cancer.
83
What is an example of a targeted therapy used to treat cancer?
Some new medicines, called targeted therapies, have exploited the overexpression of a specific protein or the mutation of a gene to develop a new medication to treat disease. One such example is the use of anti-EGF receptor medications to treat the subset of breast cancer tumors that have very high levels of the EGF protein.
84
What does a clinical trial coordinator do?
A clinical trial coordinator is the person managing the proceedings of the clinical trial. This job includes coordinating patient schedules and appointments, maintaining detailed notes, building the database to track patients (especially for long-term follow-up studies), ensuring proper documentation has been acquired and accepted, and working with the nurses and doctors to facilitate the trial and publication of the results.
85
What education is required to become a clinical trial coordinator?
A clinical trial coordinator may have a science background, like a nursing degree, or other certification. People who have worked in science labs or in clinical offices are also qualified to become a clinical trial coordinator.
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Where do clinical trial coordinators work?
These jobs are generally in hospitals; however, some clinics and doctor’s offices also conduct clinical trials and may hire a coordinator.
