Podcast
Questions and Answers
All cells in an individual, without exception, contain exactly the same genetic material and have identical requirements for gene expression.
All cells in an individual, without exception, contain exactly the same genetic material and have identical requirements for gene expression.
False (B)
Which of the following is NOT a level at which mRNA can be regulated?
Which of the following is NOT a level at which mRNA can be regulated?
- Transcriptional initiation
- Genome replication (correct)
- Splicing
- Elongation
What is the best understood mechanism of gene expression regulation?
What is the best understood mechanism of gene expression regulation?
- Nuclear export of mRNA
- mRNA splicing
- mRNA degradation
- Transcriptional initiation involving combinatorial control by transcription factors (correct)
For most genes, where does the primary regulation of gene expression occur?
For most genes, where does the primary regulation of gene expression occur?
What role do gene regulatory proteins or transcription factors play?
What role do gene regulatory proteins or transcription factors play?
Transcription factors can bind to and read the inside of the DNA helix to influence the binding or activity of RNA polymerase II.
Transcription factors can bind to and read the inside of the DNA helix to influence the binding or activity of RNA polymerase II.
Which statement best describes the information presented to transcription factors by the major groove of DNA?
Which statement best describes the information presented to transcription factors by the major groove of DNA?
How do DNA-binding proteins interact with specific base pairs without unzipping the DNA double helix?
How do DNA-binding proteins interact with specific base pairs without unzipping the DNA double helix?
A helix-turn-helix motif makes sequence-specific contacts in which groove of the DNA?
A helix-turn-helix motif makes sequence-specific contacts in which groove of the DNA?
In the context of transcription factors, ______ refers to the association between two different members of the same class, expanding the range of DNA sequences that can be recognized.
In the context of transcription factors, ______ refers to the association between two different members of the same class, expanding the range of DNA sequences that can be recognized.
What advantage does dimerization of DNA-binding proteins confer in transcriptional regulation?
What advantage does dimerization of DNA-binding proteins confer in transcriptional regulation?
The promoter region can drive transcription on its own, but it cannot dramatically increase transcription initiation from its corresponding promoter
The promoter region can drive transcription on its own, but it cannot dramatically increase transcription initiation from its corresponding promoter
Which of the following statements accurately describes enhancers?
Which of the following statements accurately describes enhancers?
How do transcription factors work cooperatively to regulate transcription?
How do transcription factors work cooperatively to regulate transcription?
Which of the following mechanisms is NOT a way that transcription factors regulate gene expression?
Which of the following mechanisms is NOT a way that transcription factors regulate gene expression?
Transcription factors are regulated solely at the level of their own gene transcription.
Transcription factors are regulated solely at the level of their own gene transcription.
What role does phosphorylation play in the regulation of transcription factors?
What role does phosphorylation play in the regulation of transcription factors?
How might post-translational modification affect transcription factor activity?
How might post-translational modification affect transcription factor activity?
What term describes the phenomenon where multiple gene regulatory proteins work together to control the rate of transcription?
What term describes the phenomenon where multiple gene regulatory proteins work together to control the rate of transcription?
Transcription ______ leads to premature termination of the RNA transcript, representing another level at which transcription can be regulated.
Transcription ______ leads to premature termination of the RNA transcript, representing another level at which transcription can be regulated.
What role do barrier sequences play?
What role do barrier sequences play?
What are insulator elements?
What are insulator elements?
Match the following DNA-binding motifs with their characteristics:
Match the following DNA-binding motifs with their characteristics:
What is a sequence-specific DNA-binding protein primarily responsible for?
What is a sequence-specific DNA-binding protein primarily responsible for?
The minor groove of DNA presents a unique signature for each base pair, allowing transcription factors to easily distinguish all base pairs.
The minor groove of DNA presents a unique signature for each base pair, allowing transcription factors to easily distinguish all base pairs.
Which of the following is an important consideration regarding the energetic cost of RNA synthesis?
Which of the following is an important consideration regarding the energetic cost of RNA synthesis?
What type of bonding primarily mediates the interaction between a DNA-binding protein and a base-pair within the DNA double helix?
What type of bonding primarily mediates the interaction between a DNA-binding protein and a base-pair within the DNA double helix?
In the helix-turn-helix motif, the ______ recognition helix makes sequence-specific contacts in the major groove of DNA.
In the helix-turn-helix motif, the ______ recognition helix makes sequence-specific contacts in the major groove of DNA.
What structural feature is characteristic of the leucine zipper DNA-binding motif?
What structural feature is characteristic of the leucine zipper DNA-binding motif?
Helix-loop-helix (HLH) motifs are structurally and functionally equivalent to helix-turn-helix motifs in DNA binding.
Helix-loop-helix (HLH) motifs are structurally and functionally equivalent to helix-turn-helix motifs in DNA binding.
What is the primary function of enhancers in transcriptional regulation?
What is the primary function of enhancers in transcriptional regulation?
What determines whether transcription factors act cooperatively or antagonistically?
What determines whether transcription factors act cooperatively or antagonistically?
Match the following scenarios with the expected level of transcription:
Match the following scenarios with the expected level of transcription:
Transcription termination is solely determined by the presence of a termination sequence in the DNA.
Transcription termination is solely determined by the presence of a termination sequence in the DNA.
How does phosphorylation control transcription factors
How does phosphorylation control transcription factors
A single factor's expression might be different in different parts of the body, what is this called?
A single factor's expression might be different in different parts of the body, what is this called?
Give two factors that are important in determining the regulation of TF's.
Give two factors that are important in determining the regulation of TF's.
______ can be reversed by binding of specific proteins to the RNA structure, allowing RNA pol to complete transcription.
______ can be reversed by binding of specific proteins to the RNA structure, allowing RNA pol to complete transcription.
Considering that a gene requires both an activator and the absence of a repressor for its expression, and given the following conditions: the activator is present, the repressor is present, and the gene is not expressed. Which of the following could explain this lack of expression?
Considering that a gene requires both an activator and the absence of a repressor for its expression, and given the following conditions: the activator is present, the repressor is present, and the gene is not expressed. Which of the following could explain this lack of expression?
A researcher is studying a novel transcription factor (TF) that contains a helix-loop-helix (HLH) motif but lacks a dimerization domain. Which of the following is the most likely functional consequence of this structural deficiency?
A researcher is studying a novel transcription factor (TF) that contains a helix-loop-helix (HLH) motif but lacks a dimerization domain. Which of the following is the most likely functional consequence of this structural deficiency?
Combinatorial control of gene expression is less efficient and provides less specificity, because only one factor works at a time.
Combinatorial control of gene expression is less efficient and provides less specificity, because only one factor works at a time.
Considering that transcription factors can be regulated post-transcriptionally, describe an experiment to elucidate whether a specific transcription factor is regulated by phosphorylation?
Considering that transcription factors can be regulated post-transcriptionally, describe an experiment to elucidate whether a specific transcription factor is regulated by phosphorylation?
If the concentration of Bicoid protein is uniform throughout the anterior-posterior axis of a developing Drosophila embryo, the expression pattern of the even-skipped gene would likely be ______ due to the lack of differential regulation by Bicoid.
If the concentration of Bicoid protein is uniform throughout the anterior-posterior axis of a developing Drosophila embryo, the expression pattern of the even-skipped gene would likely be ______ due to the lack of differential regulation by Bicoid.
Why is transcriptional initiation considered the best-understood mechanism of gene regulation?
Why is transcriptional initiation considered the best-understood mechanism of gene regulation?
Give an example of a type of gene regulation that occurs post-transcriptionally.
Give an example of a type of gene regulation that occurs post-transcriptionally.
How do transcription factors interact with the DNA helix to influence RNA polymerase II activity?
How do transcription factors interact with the DNA helix to influence RNA polymerase II activity?
What is the role of the major groove in DNA concerning gene regulation?
What is the role of the major groove in DNA concerning gene regulation?
How many contacts are generally made by a gene regulator protein with DNA?
How many contacts are generally made by a gene regulator protein with DNA?
Describe the role of the recognition helix in the helix-turn-helix motif.
Describe the role of the recognition helix in the helix-turn-helix motif.
How does the location of amino acid side chains in zinc finger proteins contribute to their function?
How does the location of amino acid side chains in zinc finger proteins contribute to their function?
Explain the function of the alpha helix in a leucine zipper motif.
Explain the function of the alpha helix in a leucine zipper motif.
In the context of DNA-binding proteins, what is the significance of heterodimerization?
In the context of DNA-binding proteins, what is the significance of heterodimerization?
Differentiate between the role of a promoter and an enhancer in RNA transcription.
Differentiate between the role of a promoter and an enhancer in RNA transcription.
What is combinatorial control of expression?
What is combinatorial control of expression?
What is required for transcription to occur?
What is required for transcription to occur?
Describe how transcription factors can alter chromatin structure to regulate gene expression.
Describe how transcription factors can alter chromatin structure to regulate gene expression.
Why do transcription factors need to be selectively activated rather than always active in every cell?
Why do transcription factors need to be selectively activated rather than always active in every cell?
Besides transcriptional regulation, how else are transcription factors regulated?
Besides transcriptional regulation, how else are transcription factors regulated?
Explain how phosphorylation can regulate the activity of transcription factors.
Explain how phosphorylation can regulate the activity of transcription factors.
Give an example of how cellular localization regulates transcription factors.
Give an example of how cellular localization regulates transcription factors.
What is the overall effect of combinatorial control?
What is the overall effect of combinatorial control?
Define transcription attenuation.
Define transcription attenuation.
How do insulator elements prevent the spurious spread of transcriptional control?
How do insulator elements prevent the spurious spread of transcriptional control?
Describe the significance of the fact that all cells in an individual contain the same genetic material.
Describe the significance of the fact that all cells in an individual contain the same genetic material.
How do cells respond effectively to environmental fluctuations?
How do cells respond effectively to environmental fluctuations?
Why is mRNA an important control point in gene expression?
Why is mRNA an important control point in gene expression?
Besides transcriptional initiation, what are other levels where mRNA can be regulated?
Besides transcriptional initiation, what are other levels where mRNA can be regulated?
Why is it important to match RNA synthesis to expression requirements?
Why is it important to match RNA synthesis to expression requirements?
How would you describe transcription factors?
How would you describe transcription factors?
In the helix-turn-helix motif, how are DNA helices angled?
In the helix-turn-helix motif, how are DNA helices angled?
What is the larger structure of homeodomain?
What is the larger structure of homeodomain?
In zinc finger proteins, how are zinc ions coordinated?
In zinc finger proteins, how are zinc ions coordinated?
What is the second subclass of zinc finger proteins?
What is the second subclass of zinc finger proteins?
How would you concisely describe leucine zipper?
How would you concisely describe leucine zipper?
Explain the structure of helix-loop-helix (HLH).
Explain the structure of helix-loop-helix (HLH).
How does dimerization of DNA-binding proteins increase contact area with DNA?
How does dimerization of DNA-binding proteins increase contact area with DNA?
When would the promoter region be considered 'upstream'?
When would the promoter region be considered 'upstream'?
How is the enhancer region positioned in terms of the promoter?
How is the enhancer region positioned in terms of the promoter?
In relation to activator and repressor, what interactions do transcription factors have?
In relation to activator and repressor, what interactions do transcription factors have?
What helps direct activators to direct local alterations in chromatin structure?
What helps direct activators to direct local alterations in chromatin structure?
How are transcription factors regulated when it comes to specific cells?
How are transcription factors regulated when it comes to specific cells?
How does post-translational regulation work?
How does post-translational regulation work?
Besides post-translational, what other regulation needs to be considered?
Besides post-translational, what other regulation needs to be considered?
Describe how the combinatorial control of transcription factors allows for a greater diversity of gene expression patterns, using the globin gene or even-skipped gene as an example.
Describe how the combinatorial control of transcription factors allows for a greater diversity of gene expression patterns, using the globin gene or even-skipped gene as an example.
Explain how post-translational modifications, such as phosphorylation, can regulate the activity and localization of transcription factors, and provide an example.
Explain how post-translational modifications, such as phosphorylation, can regulate the activity and localization of transcription factors, and provide an example.
Describe how the structure of DNA, specifically the major and minor grooves, contributes to the sequence-specific binding of transcription factors.
Describe how the structure of DNA, specifically the major and minor grooves, contributes to the sequence-specific binding of transcription factors.
Compare and contrast the roles of promoters and enhancers in regulating gene transcription by discussing their locations, functions, and orientation dependency.
Compare and contrast the roles of promoters and enhancers in regulating gene transcription by discussing their locations, functions, and orientation dependency.
Explain how dimerization and heterodimerization contribute to the diversity and specificity of DNA binding by transcription factors.
Explain how dimerization and heterodimerization contribute to the diversity and specificity of DNA binding by transcription factors.
Flashcards
Transcription Factors
Transcription Factors
Proteins that influence the binding or activity of RNA polymerase II.
Gene Regulatory Proteins
Gene Regulatory Proteins
Proteins that bind to specific DNA sequences, regulating gene transcription.
Helix-turn-helix Motif
Helix-turn-helix Motif
A DNA-binding motif, where two alpha helices connect via a short, unstructured 'turn'.
Homeodomain Motif
Homeodomain Motif
Signup and view all the flashcards
Zinc Finger Motifs
Zinc Finger Motifs
Signup and view all the flashcards
Leucine Zipper Motif
Leucine Zipper Motif
Signup and view all the flashcards
Helix-loop-helix (HLH)
Helix-loop-helix (HLH)
Signup and view all the flashcards
Dimerization of DNA-Binding Proteins
Dimerization of DNA-Binding Proteins
Signup and view all the flashcards
Heterodimerization
Heterodimerization
Signup and view all the flashcards
Promoter Region
Promoter Region
Signup and view all the flashcards
Enhancer Region
Enhancer Region
Signup and view all the flashcards
Combinatorial Control
Combinatorial Control
Signup and view all the flashcards
Synergistically
Synergistically
Signup and view all the flashcards
Transcription factor regulation
Transcription factor regulation
Signup and view all the flashcards
Selective Activation of TFs
Selective Activation of TFs
Signup and view all the flashcards
Post-transcriptional Regulation
Post-transcriptional Regulation
Signup and view all the flashcards
Transcription Attenuation
Transcription Attenuation
Signup and view all the flashcards
Insulator Elements
Insulator Elements
Signup and view all the flashcards
Barrier Sequences
Barrier Sequences
Signup and view all the flashcards
Regulation of mRNA levels
Regulation of mRNA levels
Signup and view all the flashcards
Transcriptional Initiation Regulation
Transcriptional Initiation Regulation
Signup and view all the flashcards
Hydrogen bonding in gene regulation
Hydrogen bonding in gene regulation
Signup and view all the flashcards
DNA Major Groove
DNA Major Groove
Signup and view all the flashcards
Regulation of Transcription Elongation
Regulation of Transcription Elongation
Signup and view all the flashcards
Transcriptional Repressors
Transcriptional Repressors
Signup and view all the flashcards
Chromatin Remodeling
Chromatin Remodeling
Signup and view all the flashcards
Distance Action of Enhancers
Distance Action of Enhancers
Signup and view all the flashcards
Post-translational TF Modification
Post-translational TF Modification
Signup and view all the flashcards
Regulation by TF Localization
Regulation by TF Localization
Signup and view all the flashcards
Study Notes
The Big Picture
- Cells within an individual share the same genetic material, but differ in gene expression needs.
- Cells must dynamically adjust gene expression timing and level in response to environmental changes.
- mRNA level is a key control point in gene expression regulation.
- mRNA is regulated through transcriptional initiation, elongation, splicing, nuclear export, and degradation.
- Transcriptional initiation, involving combinatorial control via transcription factors, is the most understood regulation mechanism.
Regulation of RNA Transcription
- Primary regulation occurs at RNA transcription level for most genes.
- Matching RNA synthesis to expression requirements averts expending energy to synthesize superfluous macromolecules.
- Gene regulatory proteins or transcription factors define transcription levels.
- Transcription factors contain well-characterized DNA-binding motifs.
- Transcription factors can bind to the outside of the DNA helix and influence RNA polymerase II.
DNA Grooves
- Gene regulatory proteins can interact with specific DNA base pairs without unzipping the DNA
- Interactions between a gene regulatory protein and a base-pair occur via hydrogen bonding.
- Gene regulator proteins make around 10-20 contacts with the DNA.
- The major groove presents a unique signature for each base pair.
- Transcription factors can read the outside of the DNA helix through the major or minor grooves.
- Each base on a strand can be distinguished in the major groove.
- Only AT and GC base-pairs can be distinguished in the minor groove.
Common DNA-Binding Motifs
- Helix-turn-helix is one of the simplest DNA-binding motifs.
- Two alpha helices are connected by a short unstructured stretch ("turn").
- The helices are held at a specific angle by interactions.
- The C-terminal recognition helix makes sequence-specific contacts in the major groove of DNA.
- It generally binds to DNA as symmetric dimers, where recognition helices bind to "half-sites" separated by one turn of the DNA helix.
- Homeodomain is a special case of the helix-turn-helix motif that contains a third alpha helix.
- The conserved structure suggests all homeodomains are presented to DNA in the same fashion.
- Zinc fingers coordinate one or more zinc ions with amino acid side groups.
- One subclass uses two cysteines and two histidines to coordinate zinc between an alpha helix and a 2-strand antiparallel beta sheet.
- Zinc fingers are often in tandem clusters within a DNA-binding protein.
- Another subclass coordinates two zinc ions, using four cysteines for each.
- One zinc ion stabilizes a recognition helix, and the other stabilizes a loop involved in dimerization.
- They can bind to DNA as symmetric dimers, akin to helix-turn-helix proteins.
- The Leucine zipper is an alpha helix containing a hydrophobic surface on one side.
- The protein binds DNA as a dimeric structure.
- The helix from one subunit binds to the corresponding helix in the second subunit in a coiled-coil structure via hydrophobic interactions.
- The alpha helix serves as both the dimerization region and the DNA-binding region.
- Helix-loop-helix (HLH) is not the same as helix-turn-helix.
- A short alpha helix is connected to a longer alpha helix by a flexible loop.
- The loop allows one helix to fold back and pack against the other.
- As with the leucine zipper, the HLH motif acts as both a dimerization interface and the DNA-binding region.
- Dimerization of DNA-binding proteins increases the contact area with DNA, enhancing binding and specificity.
- Heterodimerization (between two different members of the same class) expands the range of recognizable sequences.
Promoters and Enhancers
- Transcription factors act at promoter or enhancer gene regulatory regions.
- Promoters are regions where RNA polymerase and general transcription factors assemble, and are always a short distance upstream of the 5' end of a gene.
- Promoters are essential for transcription initiation, but transcription can be low.
- Promoters may be gene-specific, where their orientation is important.
- Enhancers are independent regions located outside the promoter which may be far away (up to 10s of kb) or within the gene.
- Enhancers increase transcription initiation but cannot drive transcription alone.
- Enhancers function independently of position and orientation which work with a heterologous promoter.
Transcription Factor Function
- Eukaryotic gene regulatory regions are more complex than prokaryotic ones.
- Multiple gene regulatory proteins control transcription rate in a combinatorial fashion.
- Transcription factors can work cooperatively (e.g., two activators) or antagonistically (e.g., an activator vs. a repressor).
- Cooperative interactions can synergistically increase transcription.
Transcription Factor Mechanisms
Transcription factors:
- Help unpack chromatin, which makes the gene accessible to RNA pol and the initiation complex.
- Control the recruitment of RNA pol and/or the general transcription factors to the promoter.
- Regulate the switch from initiation to elongation.
- Help recruit histone-modifying enzymes to change the local chromatin structure.
- Bend DNA to allow long-distance interactions between gene regulatory regions.
- Serve as activators or repressors.
Transcription Factor Regulation
- Transcription factors must be selectively activated and cannot be turned on in every cell all the time.
- They are regulated at the level of gene transcription via tissue-specific expression or in response to specific environmental signals, or during specific phases of the cell cycle.
- If not regulated transcriptionally, transcription factors must be regulated post-transcriptionally.
- Many transcription factors are present in an inactive state and activated by phosphorylation.
- The mitogen-activated protein kinase (MAPK) family phosphorylates many transcription factors in response to cell-surface receptor signals.
- Phosphorylation can convert an inactive form into an active from, or vice versa.
- Transcription factors have multiple sites for phosphorylation and other modifications.
- Post-translational modification may change cellular localization, not directly regulate TF activity.
- NF-AT and NF-κB held in the cytosol in an inactive sate.
- Post-translational modifications lead to release from the cytosol and translocation to the nucleus
- Nuclear Transcription factors regulate gene transcription.
- Many transcription factors are regulated via a combination of expression, activation, and localization.
Combinatorial Control
- Can generate patterns during animal development.
- Expression in one stripe is directed by one DNA module.
- Gene regulatory proteins binding to a DNA module dictate expression.
- The Even-skipped (Eve) expression in fly embryo is an example.
Additional Regulation
- RNA levels can be regulated by initiation or termination.
- Transcription attenuation prematurely terminates the RNA transcript.
- A growing RNA chain adopts a conformation that interferes with RNA polymerase activity causing RNA pol to pause, and abort transcription.
- Specific proteins can bind to the RNA structure to reverse attenuation, allowing RNA pol to complete transcription.
- Barrier sequences bind proteins to prevent the spread of heterochromatin and/or tether the DNA to the nuclear membrane.
- Insulator elements prevent DNA looping by acting as decoys or by tethering DNA to the membrane.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.