Regulation of Gene Expression Overview

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Questions and Answers

What role do specific transcription factors play in gene expression?

They regulate the transcriptional initiation directly by binding to RNA polymerase.

They control the strength and specificity of gene expression. (correct)

They function solely as coactivators.

They exclusively bind to promoter regions of all genes.

How do specific transcription factors affect transcriptional initiation?

They bind directly to DNA sequences to promote RNA polymerase activity.

They modify chromatin structure without influencing other genes.

They make indirect contacts through mediator proteins or general transcription factors. (correct)

They act only as enzymes that modify histones.

Which of the following best describes the function of mediator proteins?

They act as bridges between specific transcription factors and general transcription factors. (correct)

They are unable to interact with chromatin or histone modifications.

They bind to specific DNA sequences to regulate gene expression.

They have exclusive roles in enzymatic activities like RNA synthesis.

What is a key characteristic of specific transcription factors?

They may regulate multiple genes, each having different effects. Signup and view all the answers

Which statement about coactivators and corepressors is correct?

They may modify chromatin and interact with specific transcription factors. Signup and view all the answers

What is the primary function of enhancers in gene regulation?

To activate gene expression Signup and view all the answers

Where are regulatory elements such as enhancers and silencers typically located?

Within introns and upstream or downstream of genes Signup and view all the answers

What role do insulator elements play in gene regulation?

They prevent enhancers or silencers from affecting inappropriate genes Signup and view all the answers

What is a characteristic of response elements in gene regulation?

They mediate a response to a specific stimulus Signup and view all the answers

How do barrier sequences contribute to gene expression?

They prevent inappropriate spreading of heterochromatin Signup and view all the answers

What is the concept of 'position-effect variegation'?

It describes the phenomenon of nearby genes being silenced variably Signup and view all the answers

What is the common size range of discrete DNA sequences for regulatory elements?

6-12 bp Signup and view all the answers

What is the role of DNA-folding in the context of enhancers?

To bring enhancer regions close to the promoter Signup and view all the answers

What is the first step in gene expression that is also the most important regulated step?

Initiation of transcription Signup and view all the answers

Which of the following mechanisms primarily regulates transcriptional initiation?

Interplay of trans-acting factors and cis-acting elements Signup and view all the answers

What are cis-acting elements known to regulate?

Gene expression on the same chromosome Signup and view all the answers

How many genes in the human genome are estimated to encode DNA-binding proteins related to transcriptional regulation?

2600 Signup and view all the answers

Which of the following statements is true regarding trans-acting factors?

They can alter gene expression by binding to cis-acting elements. Signup and view all the answers

What is the primary function of RNA polymerase in gene expression?

To transcribe DNA into RNA Signup and view all the answers

Which of the following regulatory elements typically falls within promoter, enhancer, or silencer regions?

Cis-acting elements Signup and view all the answers

Which of the following is not a step at which gene expression can be regulated?

Electrophoresis of DNA Signup and view all the answers

What role do sigma factors play in prokaryotic regulation?

They are responsible for the specificity of transcriptional initiation. Signup and view all the answers

What happens to the lac operon when allolactose is present?

It causes the repressor to dissociate from the operator. Signup and view all the answers

Which of the following statements about chromatin structure in eukaryotic regulation is true?

Histone methylation can have variable effects on gene expression. Signup and view all the answers

What distinguishes general transcription factors from specific transcription factors?

Specific transcription factors bind regulatory elements on specific genes. Signup and view all the answers

What is the function of mediators in transcription regulation?

They serve as bridges and may have enzymatic activities. Signup and view all the answers

Which regulatory elements are located upstream, downstream, or within introns of genes?

Silencers Signup and view all the answers

In the context of operons, what does the term polycistronic refer to?

Clusters of genes regulated by a single promoter. Signup and view all the answers

What primarily controls the specificity of gene transcription in eukaryotes?

Enhancers and silencers Signup and view all the answers

What is the primary function of steroid agonists in relation to gene expression?

They bind to receptors and stimulate gene expression. Signup and view all the answers

What is a key characteristic of tamoxifen when it binds to the estrogen receptor in the breast?

It recruits a corepressor instead of a coactivator. Signup and view all the answers

What role does the glucocorticoid receptor play in coordinating gene expression?

It synergizes with other transcription factors to activate multiple genes. Signup and view all the answers

Which of the following is NOT a function of steroid antagonists?

Stimulating gene expression. Signup and view all the answers

What type of disease is associated with mutations in transcription factors?

Both cancer and autoimmune diseases. Signup and view all the answers

How does tamoxifen affect the endometrium?

Functions as an agonist, increasing growth risk. Signup and view all the answers

What is a common consequence of glucocorticoid signaling in relation to gene expression?

Coordination of multiple gene expressions. Signup and view all the answers

Which is an example of a glucocorticoid antagonist?

Mifepristone (RU486). Signup and view all the answers

What is the primary role of transcription factors in gene regulation?

To coordinate and regulate the expression of target genes. Signup and view all the answers

Which of the following genes is associated with the development of nail-patella syndrome?

LMX1B. Signup and view all the answers

What is the principal protein component of chylomicrons produced in the intestine?

ApoB48 Signup and view all the answers

In the editing of the APOB gene, what results from the deamination of a specific cytosine in the ApoB mRNA?

A premature stop codon Signup and view all the answers

Which regulatory elements are specific to eukaryotes and play a crucial role in gene expression?

Silencers Signup and view all the answers

Which step in gene expression is considered the fastest mechanism for regulation?

Post-translational modification Signup and view all the answers

What is a primary consequence of mutations in transcription factors?

Development of genetic diseases Signup and view all the answers

What is the main function of trans-acting factors in gene regulation?

They regulate the expression of genes on different molecules. Signup and view all the answers

Which transcription factor class promotes an increase in the rate of gene expression?

Activators Signup and view all the answers

What distinguishes the epigenetic regulation of gene expression from other forms of regulation?

It alters chromatin structure without changing the underlying DNA sequence. Signup and view all the answers

Which molecule is primarily involved in the initiation of transcription in eukaryotes?

TATA-binding protein (TBP) Signup and view all the answers

What effect do repressors have on gene expression?

They prevent RNA polymerase from binding to the promoter. Signup and view all the answers

Which of the following statements is true regarding chromatin and gene expression?

Altered chromatin structures can render genes more accessible for transcription factors. Signup and view all the answers

Why is the term 'specificity factors' often avoided in favor of 'initiation factors'?

The term can confuse various types of transcription factors. Signup and view all the answers

What is a fundamental contrast between prokaryotic and eukaryotic gene regulation mechanisms?

Prokaryotes do not have chromatin, limiting epigenetic mechanisms. Signup and view all the answers

How can the expression of a gene be quantitatively measured?

By measuring the concentration of mRNA transcribed. Signup and view all the answers

Which of the following best describes cis-acting elements in gene regulation?

They are DNA sequences that regulate the expression of genes on the same chromosome. Signup and view all the answers

What is the role of trans-acting factors in transcriptional initiation?

They are proteins that bind to cis-acting elements to facilitate recruitment of RNA polymerase. Signup and view all the answers

Which step in the expression pathway is broadly considered the most crucial for regulating gene expression?

Initiation of transcription Signup and view all the answers

What type of regulatory elements are found within larger regions such as promoters, enhancers, and silencers?

Cis-acting elements Signup and view all the answers

How many genes in the human genome are believed to encode proteins that regulate transcription?

Approximately 2600 Signup and view all the answers

What is the approximate length of cis-acting elements that regulate gene expression?

6-12 base pairs Signup and view all the answers

In the context of gene regulation, what does the term 'trans-acting' refer to?

Indirect regulation through proteins from different molecules Signup and view all the answers

Which of the following is NOT a step at which gene expression can be regulated?

Gene mutation Signup and view all the answers

What is the function of the Lac Repressor when lactose is not present?

It binds to the operator and prevents the transcription of structural genes. Signup and view all the answers

Which statement accurately describes the Shine-Dalgarno sequence in prokaryotic mRNA?

It serves as a binding site for ribosomes to facilitate translation of multiple genes. Signup and view all the answers

What is a key characteristic of prokaryotic promoters compared to eukaryotic promoters?

Prokaryotic promoters contain fewer consensus sequences. Signup and view all the answers

What happens to the Lac Operon when Allolactose is present?

Transcription of the structural genes begins as the Repressor dissociates. Signup and view all the answers

Which method allows for the measurement of gene expression for many genes simultaneously?

Gene expression microarray Signup and view all the answers

Which component of the Lac Operon serves as the binding site for RNA polymerase?

Promoter Signup and view all the answers

What is the consequence of deviations from consensus sequences in prokaryotic promoters?

It usually reduces promoter function. Signup and view all the answers

Which method is characterized by being very sensitive and accurate for measuring gene expression?

RT-PCR Signup and view all the answers

Which of the following describes the nature of eukaryotic polycistronic genes compared to prokaryotic ones?

Eukaryotic polycistronic genes use alternative ribosome binding sequences. Signup and view all the answers

What role does β-galactosidase play in the metabolism of lactose?

It is responsible for the conversion of lactose to Allolactose. Signup and view all the answers

In prokaryotic gene expression, what accounts for a substantial difference in mRNA production?

The sequence differences in promoter regions. Signup and view all the answers

How do posterior transcriptional regulatory elements differ in prokaryotes compared to eukaryotes?

They do not exist in prokaryotes. Signup and view all the answers

Which of the following best characterizes a structural gene?

It codes for any product other than a regulatory factor. Signup and view all the answers

Under what conditions is the Lac Operon actively expressed?

When lactose is available and glucose is not present. Signup and view all the answers

What is a notable feature of next-generation sequencing (RNA-seq) compared to other gene expression methods?

It can introduce biases during sequencing. Signup and view all the answers

What is the function of the repressor protein in the context of the Lac Operon?

To bind to the operator and block RNA polymerase action. Signup and view all the answers

Which of the following methods cannot detect gene expression if a corresponding probe is not present?

Gene expression microarray Signup and view all the answers

What primarily controls the binding of transcription factors to prokaryotic promoters?

The consensus sequences found in the promoter. Signup and view all the answers

What is true about the promoter size in prokaryotes compared to eukaryotes?

Prokaryotic promoters are generally less complex than eukaryotic promoters. Signup and view all the answers

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.

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.