Regulation of RNA Transcription

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Questions and Answers

Which mechanism of gene expression regulation is considered the best understood?

  • Regulation at the level of mRNA degradation.
  • Regulation of mRNA splicing and nuclear export.
  • Combinatorial control by transcription factors at transcriptional initiation. (correct)
  • Translational control of protein synthesis.

In eukaryotes, gene regulatory regions are generally less complex than those in prokaryotes.

False (B)

What is the primary function of barrier sequences in the context of transcriptional control?

inhibit the spread of heterochromatin

Sequence-specific DNA-binding proteins, known as either gene regulatory proteins or __________ factor, are key in dictating the level of transcription.

<p>transcription</p> Signup and view all the answers

Match the following DNA-binding motifs with their structural characteristics:

<p>Helix-turn-helix = Two alpha helices connected by a short unstructured stretch. Zinc finger = One or more zinc ions coordinated by amino acid side groups. Leucine zipper = Alpha helix containing a hydrophobic surface on one side. Helix-loop-helix = Short alpha helix connected to a longer alpha helix by a flexible loop.</p> Signup and view all the answers

Which of the following statements is most accurate regarding the role of enhancers in gene regulation?

<p>Enhancers can dramatically increase transcription initiation and are generally position- and orientation-independent. (D)</p> Signup and view all the answers

Transcription factors can only function as activators and cannot act as repressors of gene expression.

<p>False (B)</p> Signup and view all the answers

What structural feature of DNA allows transcription factors to interact without unzipping the DNA?

<p>major groove</p> Signup and view all the answers

The phenomenon where the growing RNA chain adopts a configuration that interferes with RNA polymerase activity, leading to premature termination of the RNA transcript, is known as transcription ________.

<p>attenuation</p> Signup and view all the answers

Match each transcription factor regulatory mechanism with its corresponding description:

<p>Phosphorylation = Activation of transcription factors by the addition of phosphate groups, often in response to cell-surface receptor signals. Combinatorial control = Multiple gene regulatory proteins working together to control the rate of transcription. Post-translational modification and localization = Regulation by changing the cellular location of the transcription factor. Dimerization = Enhancement of binding and specificity by increasing the contact area with DNA.</p> Signup and view all the answers

Which of the following is NOT a common DNA-binding motif found in transcription factors?

<p>Beta-barrel. (D)</p> Signup and view all the answers

Enhancers must directly contact the promoter to enhance transcription.

<p>False (B)</p> Signup and view all the answers

How does heterodimerization increase the range of sequences that can be recognized by transcription factors?

<p>combinatorial possibilities</p> Signup and view all the answers

The C-terminal __________ helix in the helix-turn-helix motif makes sequence-specific contacts in the major groove of DNA.

<p>recognition</p> Signup and view all the answers

Match each term related to transcription regulation with its correct description:

<p>Transcription Attenuation = Premature termination of RNA transcript. Insulator elements = Prevent spurious spread of transcriptional control. Combinatorial Control = Multiple regulatory proteins controlling transcription rate. Enhancer = Increases transcription initiation from a distance.</p> Signup and view all the answers

What is the primary role of the mitogen-activated protein kinase (MAPK) family in the regulation of transcription factors?

<p>To phosphorylate transcription factors in response to cell-surface receptor signals. (A)</p> Signup and view all the answers

A promoter is an independent region outside the RNA polymerase.

<p>False (B)</p> Signup and view all the answers

What is the function of insulator elements?

<p>prevent dna looping</p> Signup and view all the answers

The helix-loop-helix (HLH) motif acts as both a dimerization interface and the DNA-binding region, similar to the __________ zipper.

<p>leucine</p> Signup and view all the answers

Match the components to their activities:

<p>Promoter = Region where RNA polymerase assembles. Enhancer = Increases transcription from a distance. Transcription factor = influences binding or activity of RNA polymerase II. RNA Polymerase II = Synthesizes mRNA</p> Signup and view all the answers

In the context of the lac operon in bacteria, what is the effect of the presence of both glucose and lactose?

<p>The operon is repressed because glucose inhibits the production of cAMP. (A)</p> Signup and view all the answers

All cells in an individual have the same requirements for gene expression.

<p>False (B)</p> Signup and view all the answers

What type of amino acids is used to coordinate zinc ions in zinc finger motifs?

<p>cysteines and histidines</p> Signup and view all the answers

Transcription factors can serve as activators or __________.

<p>repressors</p> Signup and view all the answers

Match the step to the control of gene expression.

<p>Transcriptional Control = DNA transcription. RNA Processing Control = RNA processing. Translation Control = Translation of RNA. mRNA Degradation Control = degradation of mRNA</p> Signup and view all the answers

How does cooperative interaction impact transcription?

<p>It increases transcription synergistically (C)</p> Signup and view all the answers

Transcription factors bind to the inside of the DNA helix.

<p>False (B)</p> Signup and view all the answers

What is one of the simplest DNA-binding motifs?

<p>helix-turn-helix</p> Signup and view all the answers

The __________ is the region where RNA polymerase and the general transcription factors assemble.

<p>promoter</p> Signup and view all the answers

Match the name:

<p>Bicoid = anterior hunchback = anterior giant = posterior krüppel = posterior</p> Signup and view all the answers

Which one requires heterologous promoter

<p>Enhancer (D)</p> Signup and view all the answers

A promoter may be gene-specific.

<p>True (A)</p> Signup and view all the answers

Name factors that regulates the switch from initiation to elongation?

<p>transcription</p> Signup and view all the answers

The best understood mechanism of regulation occurs at transcriptional initiation, and involves __________ control by transcription factors.

<p>combinatorial</p> Signup and view all the answers

Match the type of regulation to its description:

<p>Tissue-specific = present in liver, but not lymphocytes expressed only in response = specific environmental signals expressed during specific = phases of cell cycle</p> Signup and view all the answers

What is the function of TF's

<p>all of the above (D)</p> Signup and view all the answers

Enhancers cannot drive transcription on its own.

<p>True (A)</p> Signup and view all the answers

How can mRNA be regulated?

<p>multiple levels</p> Signup and view all the answers

All cells in an individual contain exactly the same __________ material, but have different requirements for gene expression.

<p>genetic</p> Signup and view all the answers

Match.

<p>Homeodomain = a special case of helix-turn-helix motif Helix-loop-helix = shorter alpha helix connected to a longer alpha helix Leucine zipper = Alpha helix containing a hydrophobic surface on one side</p> Signup and view all the answers

Given that a transcription factor (TF) has three different pairing partners (A, B, and C), how many different sequences could be recognized by dimerization of this TF?

<p>6 (D)</p> Signup and view all the answers

An enhancer region can independently drive transcription of a gene without the presence of a promoter region.

<p>False (B)</p> Signup and view all the answers

Explain how the combinatorial action of gene regulatory proteins leads to the precise expression patterns observed during animal development, using the example of the Even-skipped (Eve) gene in Drosophila embryos.

<p>The distinct expression patterns are achieved by the specific combination of gene regulatory proteins that bind to the DNA module of specific genes. Pattern of expression of these proteins makes the right combination available only in one region with the DNA module dictating the expression.</p> Signup and view all the answers

A ___________ sequence binds proteins that inhibit the spread of heterochromatin and/or tether the DNA to the nuclear membrane.

<p>barrier</p> Signup and view all the answers

Match the following components with their roles in regulating gene expression:

<p>Transcription factors = Proteins that bind to specific DNA sequences, influencing the rate of transcription. Enhancers = DNA regions that can increase the transcription of a gene, even when located far from the promoter. Promoters = DNA regions where RNA polymerase and general transcription factors assemble to initiate transcription. Insulator elements = DNA sequences that prevent enhancers from influencing genes outside the intended target region.</p> Signup and view all the answers

How does the structural arrangement of DNA, specifically the major and minor grooves, facilitate sequence-specific binding by regulatory proteins?

<p>The major groove offers a more distinctive pattern of hydrogen bond donors and acceptors compared to the minor groove, enabling proteins to recognize specific DNA sequences without unwinding the helix.</p> Signup and view all the answers

What is the role of combinatorial control in gene regulation, and how does heterodimerization contribute to the diversity of regulatory outcomes?

<p>Combinatorial control allows a limited set of transcription factors to generate a vast array of regulatory outcomes. Heterodimerization expands this diversity by creating new combinations of DNA-binding specificities and regulatory functions.</p> Signup and view all the answers

Explain the functional differences between promoters and enhancers in eukaryotic gene regulation, including their mechanisms of action and relative positioning with respect to the transcription start site.

<p>Promoters are essential, located near the transcription start site, and directly bind RNA polymerase and general transcription factors. Enhancers are position- and orientation-independent, often located far from the transcription start site, and modulate transcription by interacting with the promoter via DNA looping.</p> Signup and view all the answers

Describe how the helix-turn-helix motif facilitates sequence-specific DNA binding. What are the key structural elements and their roles in recognizing and interacting with DNA?

<p>The helix-turn-helix motif contains two alpha helices, where one helix recognizes and binds to a specific DNA sequence via the major groove, while the other helix stabilizes the interaction through hydrophobic contacts. The short unstructured turn connects the two helices.</p> Signup and view all the answers

How do insulator elements prevent the inappropriate spread of heterochromatin and maintain distinct domains of gene expression? Describe two potential mechanisms by which they function.

<p>Insulator elements prevent the spread of heterochromatin by creating a barrier that inhibits the encroachment of condensed chromatin, thus maintaining distinct domains of gene expression. Potential mechanisms include tethering DNA to the nuclear membrane or acting as decoys for transcription machinery, which prevents DNA looping.</p> Signup and view all the answers

Outline the steps involved in the activation of NF-κB in response to an extracellular signal, including the roles of IκB, IKK, and the proteasome.

<p>Extracellular signals activate IKK, which phosphorylates IκB, leading to its ubiquitination and degradation by the proteasome. This degradation releases NF-κB, allowing it to translocate to the nucleus and activate gene transcription.</p> Signup and view all the answers

Describe how the expression of the Even-skipped gene in Drosophila embryos is regulated by combinatorial control. What roles do regulatory proteins such as Bicoid, Hunchback, Giant, and Krüppel play?

<p>The <em>Even-skipped</em> gene's expression is regulated by the combinatorial action of Bicoid and Hunchback (activators) and Giant and Krüppel (repressors). The specific combination and concentration of these proteins determine the boundaries of each stripe by binding to specific DNA modules.</p> Signup and view all the answers

Explain how transcription attenuation regulates gene expression, and under what circumstances is it reversed by binding specific proteins to the RNA structure?

<p>Transcription attenuation leads to premature termination of the RNA transcript when the growing RNA chain forms a structure that interferes with RNA polymerase activity. This process can be reversed when specific proteins bind to this RNA structure, stabilizing it and allowing RNA polymerase to complete transcription.</p> Signup and view all the answers

How do post-translational modifications, such as phosphorylation, regulate the activity and localization of transcription factors?

<p>Phosphorylation of transcription factors can either activate or inactivate them by altering their ability to bind DNA, interact with other proteins, or translocate to the nucleus, thereby modulating gene expression. It can also regulate cellular localization, affecting access to target genes.</p> Signup and view all the answers

Explain the concept of synergistic activation by transcription factors and how it differs from additive effects. What mechanisms enable synergistic gene regulation?

<p>Synergistic activation occurs when the combined effect of multiple transcription factors on gene expression is greater than the sum of their individual effects. This is often enabled through cooperative binding or by inducing conformational changes that significantly enhance transcriptional activity.</p> Signup and view all the answers

Describe the role of general transcription factors in eukaryotic transcription initiation. How do they interact with RNA polymerase II and the promoter region?

<p>General transcription factors, such as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH, are essential for recruiting and positioning RNA polymerase II at the promoter. They sequentially bind to the promoter region, forming a preinitiation complex that enables transcription to begin.</p> Signup and view all the answers

What are the key differences between the leucine zipper and helix-loop-helix (HLH) motifs in DNA-binding proteins? How do these structural differences affect their function and dimerization?

<p>Leucine zippers feature alpha helices with hydrophobic surfaces that mediate dimerization, while HLH motifs have a short alpha helix, a flexible loop, and a longer alpha helix, allowing one helix to fold back and pack against the other. The leucine zipper serves as the dimerization and the DNA binding motif. The HLH motif acts as a dimerization interface and the DNA-binding region.</p> Signup and view all the answers

Explain the role of chromatin remodeling complexes in transcription. How do they alter chromatin structure to facilitate or inhibit gene expression?

<p>Chromatin remodeling complexes use ATP hydrolysis to alter DNA-histone contacts, making DNA more or less accessible to transcription factors and RNA polymerase. They can reposition nucleosomes, evict them, or replace them with variant histones to regulate gene expression.</p> Signup and view all the answers

How does DNA methylation influence gene expression? What enzymes are involved, and what regions of the genome are typically methylated and why?

<p>DNA methylation typically leads to gene silencing by recruiting proteins that condense chromatin or directly interfering with transcription factor binding. DNA methyltransferases (DNMTs) catalyze this process, often targeting CpG islands in promoter regions to regulate gene expression.</p> Signup and view all the answers

Describe the function of the mediator complex in eukaryotic transcription. How does it facilitate communication between transcription factors and RNA polymerase II?

<p>The mediator complex acts as a bridge between transcription factors bound to enhancers and the RNA polymerase II complex at the promoter. It integrates regulatory signals and transmits them to RNA polymerase II, influencing the rate of transcription initiation.</p> Signup and view all the answers

What distinguishes a "gene regulatory protein" from other proteins that might interact with DNA? What characteristics are unique to gene regulatory proteins?

<p>Gene regulatory proteins specifically bind to DNA sequences to control transcription rates, unlike structural or enzymatic proteins. Features include DNA-binding motifs, regulatory domains, and the ability to interact with other proteins in a combinatorial fashion.</p> Signup and view all the answers

Explain how different globin genes are expressed at different developmental stages in mammals. What mechanisms ensure this temporal regulation?

<p>Different globin genes are expressed at different stages of development. This occurs thanks to a 100,000 nucleotide pair locus control region which dictates which genes are expressed in the cluster of globin genes.</p> Signup and view all the answers

What are the steps involved in activation of transcription factors in cells and how is the process regulated?

<p>Transcription factors must be activated (cannot have every TF turned on at the same time). TF's can be post transcriptionally modified. The mitogen activated protein kinase (MAPK) family is important for phosphorylating a variety of TF's in response to signals from cell-surface receptors. Phosphorylation converts an inactive form into an active form, or vice versa</p> Signup and view all the answers

What are the key structural components of a zinc finger motif, and how does this motif facilitate DNA binding?

<p>Zinc finger motifs use zinc ions to coordinate amino acid side chains, stabilizing a structure with an alpha helix and a beta sheet. The alpha helix inserts into the major groove of DNA, allowing sequence-specific contacts for binding.</p> Signup and view all the answers

How do transcription factors interact with each other to fine-tune gene expression in response to varying cellular conditions?

<p>Transcription factors interact both physically and functionally, forming complexes that synergistically or antagonistically modulate gene transcription. This interaction enables flexible and precise responses to diverse cellular conditions.</p> Signup and view all the answers

How do transcription factors coordinate with histone-modifying enzymes to regulate local chromatin structure?

<p>Transcription factors recruit histone-modifying enzymes to specific genomic locations, leading to histone acetylation (activation) or deacetylation/methylation (repression) to control DNA accessibility and, consequently, gene expression.</p> Signup and view all the answers

Dimerization of transcription factors increases binding affinity and specificity. Explain the different outcomes with homodimerization versus heterodimerization.

<p>Homodimerization increases binding affinity and specificity while heterodimerization expands the range of sequences that can be recognized, offering increased regulatory diversity.</p> Signup and view all the answers

How can the same transcription factor function as an activator in some cellular contexts but as a repressor in others?

<p>A transcription factor's role depends on interactions with co-activators or co-repressors, post-translational modifications, and the specific promoter context of the target gene. These factors determine whether it enhances or inhibits transcription.</p> Signup and view all the answers

If a transcription factor is NOT regulated at the level of transcription, what other mechanisms regulate its activity and function?

<p>If not regulated at the transcriptional level, transcription factors can be regulated post-transcriptionally by phosphorylation, cellular location, or interaction with other proteins.</p> Signup and view all the answers

Transcription factors need to be selectively activated in a cell at any given time. How does a cell solve the “chicken and egg” problem of selectively regulating the transcription of TF genes?

<p>This is solved by other mechanisms such as tissue-specific expression. Some are expressed only in response to specific environmental signals others are expressed during specific phases of cell cycle.</p> Signup and view all the answers

Flashcards

What are gene regulatory proteins or transcription factors?

Sequence-specific DNA-binding proteins that influence transcription levels.

What is a Helix-turn-helix?

A DNA-binding motif with two alpha helices connected by a short unstructured stretch.

What is a Homeodomain?

A helix-turn-helix variant including a third alpha helix.

What are Zinc fingers?

DNA-binding motif coordinated by zinc ions and amino acid side groups like cysteines and histidines.

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What is a Leucine zipper?

A DNA-binding motif with an alpha helix containing a hydrophobic surface on one side.

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What is Helix-loop-helix (HLH)?

A DNA-binding motif where a short alpha helix is connected to a longer one by a flexible loop.

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The role of Dimerization of DNA-binding proteins?

Enhancement of binding and specificity by increasing the contact area with DNA.

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What is Heterodimerization?

Increasing the range of recognized sequences using different members of the same class.

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What is the Promoter?

Region where RNA polymerase and general transcription factors assemble.

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What is the Enhancer?

Independent region outside the promoter that dramatically increases transcription initiation.

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What is Combinatorial control of expression?

Control of transcription rate using multiple gene regulatory proteins.

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What is the role of Transcription factors (TF)?

Transcription factors (TFs) regulate gene expression via a variety of mechanisms, including activators or repressors.

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What is Transcriptional Regulation?

RNA levels regulated at the level of initiation or termination.

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What is Transcription Attenuation?

Leads to premature termination of the RNA transcript

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What are Barrier sequences and Insulator elements?

They prevent spurious spread of transcriptional control.

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Where does gene expression regulation occur?

Occurs at the level of mRNA; regulation is the first place where it can occur.

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What mechanism regulates gene expression?

The best understood mechanism; involves combinatorial control by transcription factors.

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Why regulate RNA transcription?

Matching RNA synthesis to needs avoids wasting energy on unneeded molecules.

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How do Transcription factors regulate genes?

Can bind to and read the DNA helix, influencing RNA polymerase II activity.

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What is the major groove of DNA?

Presents a unique pattern for each base pair, allowing protein interaction.

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How to DNA-binding proteins interact?

Proteins can interact without unwinding DNA; accomplished through hydrogen bonding.

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What level of transcription does Promotor perform?

Required for transcription initiation; may only have low transcription levels.

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How do Eukaryotic gene regulatory regions compare?

Eukaryotic regions are more complex than prokaryotic regulatory regions.

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Gene Expression Mechanisms?

May unpack chromatin, control RNA polymerase recruitment, or regulate elongation.

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When are transcription factors activated?

Transcription factors must be selectively activated.

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Regulation of Transcription Factors?

Post-translational modification may change cellular location.

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Study Notes

  • The most well understood regulation mechanism is transcription initiation using combinatorial control of transcription factors.

Combinatorial Control

  • Regulation can be achieved by the combined use of repressors and activators that enables bacteria sophisticated control of transcription .
  • In animal development, combinatorial control generates patterns.
  • Expression in one stripe is directed by one DNA module.
  • Gene regulatory proteins bind to a DNA module to dictate expression.
  • The pattern of expression of gene regulatory proteins makes the right combination available only in one stripe.
  • Similar combinatorial logic may regulate the expression of globin genes in mammals.

Gene Types for TF Regulation

  • Cells in different places in an embryo can sense their locations and activate/express different TFs.
  • During development, cells can receive different soluble signals that direct TF expression/activation

Regulation of TF

  • If transcription factors are not regulated transcriptionally, they are done so post-transcriptionally.
  • Many transcription factors are present in an inactive state and are activated by phosphorylation.
  • The Mitogen Activated Protein Kinase (MAPK) family phosphorylates a variety of TFs in response to signals from cell-surface receptors.
  • Phosphorylation converts an inactive form into an active form, or vice versa
  • Transcription factors often have multiple sites for phosphorylation and other modifications, thus acting as molecular integrators

NF-AT and NF-kB

  • NF-AT and NF-kB are held in the cytosol in “inactive” states,
  • Post-translational modifications lead to release from the cytosol and translocation to the nucleus, where it then regulates gene transcription.
  • Many transcription factors are regulated by combined expression, activation, and localization.

p53

  • Is modified at over 20 different sites within its structure.

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