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What role do specific transcription factors play in gene expression?
What role do specific transcription factors play in gene expression?
How do specific transcription factors affect transcriptional initiation?
How do specific transcription factors affect transcriptional initiation?
Which of the following best describes the function of mediator proteins?
Which of the following best describes the function of mediator proteins?
What is a key characteristic of specific transcription factors?
What is a key characteristic of specific transcription factors?
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Which statement about coactivators and corepressors is correct?
Which statement about coactivators and corepressors is correct?
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What is the primary function of enhancers in gene regulation?
What is the primary function of enhancers in gene regulation?
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Where are regulatory elements such as enhancers and silencers typically located?
Where are regulatory elements such as enhancers and silencers typically located?
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What role do insulator elements play in gene regulation?
What role do insulator elements play in gene regulation?
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What is a characteristic of response elements in gene regulation?
What is a characteristic of response elements in gene regulation?
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How do barrier sequences contribute to gene expression?
How do barrier sequences contribute to gene expression?
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What is the concept of 'position-effect variegation'?
What is the concept of 'position-effect variegation'?
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What is the common size range of discrete DNA sequences for regulatory elements?
What is the common size range of discrete DNA sequences for regulatory elements?
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What is the role of DNA-folding in the context of enhancers?
What is the role of DNA-folding in the context of enhancers?
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What is the first step in gene expression that is also the most important regulated step?
What is the first step in gene expression that is also the most important regulated step?
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Which of the following mechanisms primarily regulates transcriptional initiation?
Which of the following mechanisms primarily regulates transcriptional initiation?
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What are cis-acting elements known to regulate?
What are cis-acting elements known to regulate?
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How many genes in the human genome are estimated to encode DNA-binding proteins related to transcriptional regulation?
How many genes in the human genome are estimated to encode DNA-binding proteins related to transcriptional regulation?
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Which of the following statements is true regarding trans-acting factors?
Which of the following statements is true regarding trans-acting factors?
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What is the primary function of RNA polymerase in gene expression?
What is the primary function of RNA polymerase in gene expression?
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Which of the following regulatory elements typically falls within promoter, enhancer, or silencer regions?
Which of the following regulatory elements typically falls within promoter, enhancer, or silencer regions?
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Which of the following is not a step at which gene expression can be regulated?
Which of the following is not a step at which gene expression can be regulated?
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What role do sigma factors play in prokaryotic regulation?
What role do sigma factors play in prokaryotic regulation?
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What happens to the lac operon when allolactose is present?
What happens to the lac operon when allolactose is present?
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Which of the following statements about chromatin structure in eukaryotic regulation is true?
Which of the following statements about chromatin structure in eukaryotic regulation is true?
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What distinguishes general transcription factors from specific transcription factors?
What distinguishes general transcription factors from specific transcription factors?
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What is the function of mediators in transcription regulation?
What is the function of mediators in transcription regulation?
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Which regulatory elements are located upstream, downstream, or within introns of genes?
Which regulatory elements are located upstream, downstream, or within introns of genes?
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In the context of operons, what does the term polycistronic refer to?
In the context of operons, what does the term polycistronic refer to?
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What primarily controls the specificity of gene transcription in eukaryotes?
What primarily controls the specificity of gene transcription in eukaryotes?
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What is the primary function of steroid agonists in relation to gene expression?
What is the primary function of steroid agonists in relation to gene expression?
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What is a key characteristic of tamoxifen when it binds to the estrogen receptor in the breast?
What is a key characteristic of tamoxifen when it binds to the estrogen receptor in the breast?
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What role does the glucocorticoid receptor play in coordinating gene expression?
What role does the glucocorticoid receptor play in coordinating gene expression?
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Which of the following is NOT a function of steroid antagonists?
Which of the following is NOT a function of steroid antagonists?
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What type of disease is associated with mutations in transcription factors?
What type of disease is associated with mutations in transcription factors?
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How does tamoxifen affect the endometrium?
How does tamoxifen affect the endometrium?
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What is a common consequence of glucocorticoid signaling in relation to gene expression?
What is a common consequence of glucocorticoid signaling in relation to gene expression?
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Which is an example of a glucocorticoid antagonist?
Which is an example of a glucocorticoid antagonist?
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What is the primary role of transcription factors in gene regulation?
What is the primary role of transcription factors in gene regulation?
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Which of the following genes is associated with the development of nail-patella syndrome?
Which of the following genes is associated with the development of nail-patella syndrome?
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What is the principal protein component of chylomicrons produced in the intestine?
What is the principal protein component of chylomicrons produced in the intestine?
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In the editing of the APOB gene, what results from the deamination of a specific cytosine in the ApoB mRNA?
In the editing of the APOB gene, what results from the deamination of a specific cytosine in the ApoB mRNA?
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Which regulatory elements are specific to eukaryotes and play a crucial role in gene expression?
Which regulatory elements are specific to eukaryotes and play a crucial role in gene expression?
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Which step in gene expression is considered the fastest mechanism for regulation?
Which step in gene expression is considered the fastest mechanism for regulation?
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What is a primary consequence of mutations in transcription factors?
What is a primary consequence of mutations in transcription factors?
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What is the main function of trans-acting factors in gene regulation?
What is the main function of trans-acting factors in gene regulation?
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Which transcription factor class promotes an increase in the rate of gene expression?
Which transcription factor class promotes an increase in the rate of gene expression?
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What distinguishes the epigenetic regulation of gene expression from other forms of regulation?
What distinguishes the epigenetic regulation of gene expression from other forms of regulation?
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Which molecule is primarily involved in the initiation of transcription in eukaryotes?
Which molecule is primarily involved in the initiation of transcription in eukaryotes?
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What effect do repressors have on gene expression?
What effect do repressors have on gene expression?
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Which of the following statements is true regarding chromatin and gene expression?
Which of the following statements is true regarding chromatin and gene expression?
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Why is the term 'specificity factors' often avoided in favor of 'initiation factors'?
Why is the term 'specificity factors' often avoided in favor of 'initiation factors'?
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What is a fundamental contrast between prokaryotic and eukaryotic gene regulation mechanisms?
What is a fundamental contrast between prokaryotic and eukaryotic gene regulation mechanisms?
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How can the expression of a gene be quantitatively measured?
How can the expression of a gene be quantitatively measured?
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Which of the following best describes cis-acting elements in gene regulation?
Which of the following best describes cis-acting elements in gene regulation?
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What is the role of trans-acting factors in transcriptional initiation?
What is the role of trans-acting factors in transcriptional initiation?
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Which step in the expression pathway is broadly considered the most crucial for regulating gene expression?
Which step in the expression pathway is broadly considered the most crucial for regulating gene expression?
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What type of regulatory elements are found within larger regions such as promoters, enhancers, and silencers?
What type of regulatory elements are found within larger regions such as promoters, enhancers, and silencers?
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How many genes in the human genome are believed to encode proteins that regulate transcription?
How many genes in the human genome are believed to encode proteins that regulate transcription?
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What is the approximate length of cis-acting elements that regulate gene expression?
What is the approximate length of cis-acting elements that regulate gene expression?
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In the context of gene regulation, what does the term 'trans-acting' refer to?
In the context of gene regulation, what does the term 'trans-acting' refer to?
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Which of the following is NOT a step at which gene expression can be regulated?
Which of the following is NOT a step at which gene expression can be regulated?
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What is the function of the Lac Repressor when lactose is not present?
What is the function of the Lac Repressor when lactose is not present?
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Which statement accurately describes the Shine-Dalgarno sequence in prokaryotic mRNA?
Which statement accurately describes the Shine-Dalgarno sequence in prokaryotic mRNA?
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What is a key characteristic of prokaryotic promoters compared to eukaryotic promoters?
What is a key characteristic of prokaryotic promoters compared to eukaryotic promoters?
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What happens to the Lac Operon when Allolactose is present?
What happens to the Lac Operon when Allolactose is present?
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Which method allows for the measurement of gene expression for many genes simultaneously?
Which method allows for the measurement of gene expression for many genes simultaneously?
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Which component of the Lac Operon serves as the binding site for RNA polymerase?
Which component of the Lac Operon serves as the binding site for RNA polymerase?
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What is the consequence of deviations from consensus sequences in prokaryotic promoters?
What is the consequence of deviations from consensus sequences in prokaryotic promoters?
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Which method is characterized by being very sensitive and accurate for measuring gene expression?
Which method is characterized by being very sensitive and accurate for measuring gene expression?
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Which of the following describes the nature of eukaryotic polycistronic genes compared to prokaryotic ones?
Which of the following describes the nature of eukaryotic polycistronic genes compared to prokaryotic ones?
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What role does β-galactosidase play in the metabolism of lactose?
What role does β-galactosidase play in the metabolism of lactose?
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In prokaryotic gene expression, what accounts for a substantial difference in mRNA production?
In prokaryotic gene expression, what accounts for a substantial difference in mRNA production?
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How do posterior transcriptional regulatory elements differ in prokaryotes compared to eukaryotes?
How do posterior transcriptional regulatory elements differ in prokaryotes compared to eukaryotes?
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Which of the following best characterizes a structural gene?
Which of the following best characterizes a structural gene?
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Under what conditions is the Lac Operon actively expressed?
Under what conditions is the Lac Operon actively expressed?
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What is a notable feature of next-generation sequencing (RNA-seq) compared to other gene expression methods?
What is a notable feature of next-generation sequencing (RNA-seq) compared to other gene expression methods?
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What is the function of the repressor protein in the context of the Lac Operon?
What is the function of the repressor protein in the context of the Lac Operon?
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Which of the following methods cannot detect gene expression if a corresponding probe is not present?
Which of the following methods cannot detect gene expression if a corresponding probe is not present?
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What primarily controls the binding of transcription factors to prokaryotic promoters?
What primarily controls the binding of transcription factors to prokaryotic promoters?
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What is true about the promoter size in prokaryotes compared to eukaryotes?
What is true about the promoter size in prokaryotes compared to eukaryotes?
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Study Notes
Regulation of Gene Expression
- Gene expression can be regulated at every step of the pathway including:
- Transcription initiation
- Transcript processing
- mRNA degradation
- Translation
- Post-translational processing
- Protein degradation
Transcription Initiation
- The most important regulated step in gene expression
- The human genome contains ~2600 genes encoding DNA-binding proteins, most are presumed to be transcriptional regulators (>10% of human genes are involved in regulating transcription)
Regulation of Transcriptional Initiation
- There are two main mechanisms
- Interplay of trans-acting factors and cis-acting elements to control RNA polymerase recruitment.
- All genes contain consensus sequences called "cis-acting elements" which regulate the gene's expression.
- Cis-acting elements are bound by protein "trans-acting factors" which affect the recruitment of RNA polymerase.
- These mechanisms are important in both prokaryotes and eukaryotes.
- cis-acting elements: short discreet DNA sequences that play a role in regulating a gene on the same chromosome. They are found within larger regulatory regions such as promoters, enhancers and silencers.
-
trans-acting elements: regulation is conferred by a molecule different than that being regulated. They include enhancers and silencers.
- Enhancers: activate transcription and can be located upstream, downstream, or within introns of genes. Rarely found in exons.
- Silencers: repress transcription. They are usually location and orientation non-specific and can be > 106 bp from the gene.
- They can regulate transcription initiation by DNA-folding, which brings the region into closer proximity of the promoter.
- Interplay of trans-acting factors and cis-acting elements to control RNA polymerase recruitment.
Eukaryotic Regulatory Elements
- Discrete DNA sequences of 6-12 bp
- Bind transcription factors
- Found in promoters, enhancers or silencers
- Response elements: mediate a response to a stimuli
- Insulator elements: prevent enhancers or silencers from regulating the inappropriate genes
-
Barrier Sequences: prevent heterochromatin from spreading inappropriately
- Heterchromatin can vary in size in different cells and may cause genes nearby the heterochromatin region to be silenced inappropriately.
Identifying Regulatory Elements
- Reporter Assays: mutational analysis of a regulatory region can be used to identify specific regulatory elements.
Specific Transcription Factors
- Thousands of factors that bind regulatory elements and control:
- Strength of expression
- Specificity of expression (cell type and temporal specificity)
- Response to stimuli
- Only regulate specific gene(s)
- May regulate many different genes, sometimes having drastically different effects
Mediator Proteins
- Specific transcription factors affect transcriptional initiation indirectly.
- They make contacts with either:
- General transcription factors, or
- Mediator proteins
- Act as "bridges” between the general transcription factors and don't bind to specific DNA sequences.
- May have enzymatic activity (HATs, HDACs, histone modifications, chromatin remodelling).
- They act as coactivators or corepressors.
Steroid Agonists vs. Antagonists
-
Agonists: Bind to a receptor and stimulate gene expression.
- Examples: most endogenous steroids, Dexamethasone (a synthetic glucocorticoid agonist).
-
Antagonists: Block the activity of the endogenous steroid by competitive binding to the receptor and repress gene expression and/or block activation
- Examples: Mifepristone (RU486) – a glucocorticoid and progesterone antagonist.
Treatment of Breast Cancer by Tamoxifen
- Growth of some breast cancers depends on estrogen signaling
- Tamoxifen:
- An estrogen antagonist in the breast.
- Estrogen Receptor bound to Tamoxifen recruits a corepressor instead of a coactivator, stopping cell division
- An estrogen agonist in the endometrium.
- Estrogen Receptor bound to Tamoxifen recruits a coactivator, increasing the risk of endometrial cancer.
Coordinated Gene Expression
- A single transcription factor can coordinate the expression of many genes.
- Example: Upon glucocorticoid signaling, the glucocorticoid receptor works with other factors to activate all genes.
- This is a mechanism for:
- Coordinated expression of many genes
- Cell-type specificity because the glucocorticoid receptor can activate different sets of genes in different cell types, depending on the transcription factors expressed in that cell type.
Transcription Factors and Disease
- Mutations in transcription factors are associated with many diseases.
- Cancer
- Many proto-oncogenes are transcription factors (c-myc, c-jun, c-fos)
- Autoimmune
- Polyendocrinopathy Syndrome (AIRE)
- Developmental
- Nail-patella syndrome (LMX1B)
- Cleidocranial dysplasia (RUNX2)
- Bicuspid aortic valve (GATA4)
- Synpolydactyly (HOXD13)
- Diabetes
- Maturity Onset Diabetes of the Young (MODY) (HNF1α, HNF1β, HNF4α, PDX1, NEUROD1)
Prokaryotic Regulation
- Promoters: the only regulatory region
- Few regulatory elements / consensus sequences
- Sigma factors: specificity and transcriptional initiation
- Co-repressors & Inducers: ligands that act via a repressor
- Co-Activators & Repressors: ligands that act via an activator
-
Operons: polycistronic clusters of genes regulated by a single promoter
- Coordinated regulation
-
Lac Operon: active when Lactose is available and Glucose is not
- Allolactose: the inducer that causes repressors to dissociate from the operator
- cAMP: the co-activator that causes CAP proteins to bind to the CAP site
Eukaryotic Regulation: Chromatin Structure
- DNA Methylation: silencing, permanent
- Histone Acetylation: activating, dynamic
- Histone Methylation: variable, dynamic
- ATP-Dependent Chromatin Remodeling (SWI/SNF): removes/modifies nucleosomes.
Summary
-
Regulatory Regions:
- Promoters: immediately 5' of every gene, initiate transcription via the TATA Box, Inr Sequence (bind Basal/General Transcription Factors), and control specificity via other regulatory elements that bind Specific Transcription Factors.
- Enhancers, Silencers: can be located upstream, downstream, in introns of some genes, and control specificity via other regulatory elements that bind Specific Transcription Factors. Enhancers activate, Silencers repress.
- Regulatory Elements: Response elements mediate a response to a stimuli
- Reporter Assays: used to identify positive and negative regulatory elements
-
Transcription Factors:
- General: Assemble around a TATA or Inr Sequence on ALL genes, directly recruit RNA polymerase.
- Specific: Bind at other regulatory elements only on specific genes, indirectly recruit RNA polymerase and may act synergistically. They contact DNA through DNA-binding domains, which form sequence-specific bonds with bases.
- Mediator Proteins: “Bridges” that may have enzymatic activity and act as coactivators or corepressors.
Gene Expression Regulation
- Gene expression can be regulated at any stage of the gene expression pathway
- The most important regulated step is transcriptional initiation
- The human genome contains around 2600 genes that encode DNA-binding proteins, many of which are presumed to be transcriptional regulators
Transcriptional Initiation
- Two major mechanisms regulate transcriptional initiation:
- Interplay between trans-acting factors and cis-acting elements to control RNA polymerase recruitment.
- Alteration of chromatin structures to control accessibility of the gene to transcription factors and RNA polymerase.
Cis-Acting Elements
- Cis-acting elements are short discreet DNA sequences
- They regulate a gene on the same chromosome
- They are found in regulatory regions such as promoters, enhancers and silencers
- They bind to trans-acting factors which are proteins that regulate gene expression
Trans-Acting Factors
- These are proteins that regulate gene expression on a different molecule, often a DNA strand within a chromosome.
- They include transcription factors, activators and repressors.
- The activity of these proteins may be controlled by other molecules.
Measuring Gene Expression
- Gene expression can be measured by quantifying mRNA levels.
- Common methods include: Northern Blot, RT-PCR, gene expression microarray and Next-generation sequencing (RNA-seq).
Prokaryotic Gene Expression
- Prokaryotic promoters are regulatory regions found upstream of the transcription start site
- They are the only regulatory regions used in prokaryotes.
- Promoter sequences influence the rate of transcription.
- They contain binding sites for transcription factors.
Lac Operon
- The Lac operon is a group of genes related to lactose metabolism in bacteria.
- It contains a promoter, an operator, three structural genes and one regulatory gene (Lac I) encoding a repressor.
- The Lac repressor binds to the operator, preventing transcription.
- The presence of lactose induces the expression of the Lac operon via the inducer allolactose.
- Allolactose binds to the repressor and causes it to dissociate from the operator, allowing transcription to proceed.
Apolipoprotein B (ApoB)
- The APOB gene encodes apolipoprotein B (ApoB), a protein component of lipoproteins.
- ApoB is produced in the liver and the intestine.
- The liver produces ApoB100, a full-length protein.
- The intestine produces ApoB48, a truncated protein that is only 48% the size of the liver protein.
- ApoB48 is produced due to the editing of the APOB mRNA in intestinal cells.
- This editing involves deamination of a specific cytosine in the APOB mRNA, resulting in a premature stop codon, causing the creation of a truncated protein.
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Description
This quiz explores the different mechanisms involved in the regulation of gene expression, particularly focusing on transcription initiation. Learn about the roles of cis-acting elements and trans-acting factors, and how they work together to control RNA polymerase recruitment. Perfect for students interested in molecular biology and genetics.
