Gene Regulation and Expression

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Questions and Answers

What is the primary reason that gene expression must be regulated?

To allow different cell types to express different sets of genes. (correct)

To increase the total amount of DNA in a cell.

To prevent gene transcription entirely.

To ensure all cells produce the same proteins.

Which of the following is an example of long-term gene regulation?

A cell's adjustment to a short-term exposure to a growth factor.

The determination of a cell's tissue-specific identity which is passed on to daughter cells. (correct)

A cell's response to a sudden change in the nutrient level.

An immediate increase in protein production due to a quick hormonal signal.

At which level is gene expression NOT regulated?

Epigenetic/Chromatin remodelling

Transcriptional

Post-translational (correct)

Translational

What is the role of transcription factors in gene regulation?

To bind to regulatory DNA sequences and control the rate of transcription. Signup and view all the answers

Which of the following processes is associated with chromatin remodeling in gene regulation?

Modifications of histone proteins, including acetylation. Signup and view all the answers

How is tissue-specific gene expression primarily achieved?

Through specific combinations of regulatory DNA sequences and transcription factors. Signup and view all the answers

During which cellular process does short-term gene regulation typically play a role?

A cell's reaction to a growth factor or hormone. Signup and view all the answers

What is one of the roles of DNA regulatory sequences in controlling transcription?

They provide sites for transcription factors to bind, controlling the rate of transcription. Signup and view all the answers

What is the primary role of transcription factors in the initiation of transcription?

They guide RNA polymerase II to the core promoter region Signup and view all the answers

Which event marks the termination of transcription?

The encounter of a specific termination signal by RNA polymerase II Signup and view all the answers

What is the role of co-activators in transcription?

They enhance gene transcription by interacting with transcription factors Signup and view all the answers

Which domain of a transcription factor is responsible for recognizing specific DNA sequences?

DNA-binding domain Signup and view all the answers

What is the role of the TATA-binding protein (TBP)?

It recognizes and binds to specific DNA sequences called TATA boxes Signup and view all the answers

During transcription elongation, what is the function of RNA polymerase II?

It creates a transcription bubble, and synthesizes a complimentary RNA using a DNA template Signup and view all the answers

What distinguishes a co-repressor from a co-activator?

Co-repressors promote gene silencing while co-activators increase gene transcription. Signup and view all the answers

The specificity of a transcription factor for a particular DNA sequence is principally determined by which characteristic?

The amino acid sequence of the DNA binding domain Signup and view all the answers

What is the purpose of the phosphorylation of RNA polymerase II at RBP1?

To initiate transcription Signup and view all the answers

Which of the following statements regarding transcription factors is FALSE?

Most transcription factors work in isolation and do not recruit other proteins. Signup and view all the answers

What is the primary effect of histone acetylation on DNA?

Disruption of electrostatic interactions with histones. Signup and view all the answers

Which of the following protein domains is associated with the recognition of acetylated histones?

Bromodomain. Signup and view all the answers

What is the immediate consequence of recruiting histone deacetylases (HDACs) to gene promoters?

Repression of gene activity. Signup and view all the answers

How do transcription activators facilitate gene expression via chromatin modifications?

By recruiting histone acetyltransferases and chromatin remodeling complexes. Signup and view all the answers

What role do transcription repressors play in gene expression according to the text?

They inhibit gene transcription by inducing chromatin condensation. Signup and view all the answers

Why is tissue-specific regulation of transcription necessary?

To allow different cells to express a unique set of genes. Signup and view all the answers

What distinguishes euchromatin from heterochromatin in the context of gene transcription?

Euchromatin is open and transcriptionally active, while heterochromatin is condensed and inactive. Signup and view all the answers

Which of the following modifications results in the unraveling of chromatin?

Histone acetylation. Signup and view all the answers

What is the primary role of euchromatin in gene expression?

Allowing RNA Pol II and necessary transcription factors to bind to DNA. Signup and view all the answers

How do transcriptional repressors that bind to silencer elements function?

By binding to DNA and directly inhibiting the recruitment of RNA Pol II. Signup and view all the answers

What is the main effect of nucleosomes on gene transcription when they are tightly packed?

They prevent the transcription complex from accessing the gene promoter. Signup and view all the answers

What is the primary role of basic transcription factors?

To recruit RNA Polymerase II to the gene promoter. Signup and view all the answers

What are the key mechanisms by which chromatin 'opens up' to permit gene transcription?

Nucleosome displacement and histone acetylation. Signup and view all the answers

Which of the following is a characteristic of specific transcription factors?

They exhibit tissue-specificity in their action. Signup and view all the answers

Where is the core promoter typically located in relation to a gene?

Upstream of the gene, within 60-120 base pairs. Signup and view all the answers

Which of the following is a characteristic of histones?

They are positively charged proteins, rich in lysine and arginine that can undergo covalent modifications. Signup and view all the answers

What is the direct effect of histone acetylation on the charge of histones?

It reduces the positive charge of histones. Signup and view all the answers

What is a key feature of enhancers and silencers?

They can regulate gene expression from a distance. Signup and view all the answers

How do enhancers and silencers physically interact with the core promoter to regulate gene transcription?

Through long loops in DNA, mediated by proteins like cohesins, bringing them in close proximity. Signup and view all the answers

What enzymatic activity is associated with histone acetyltransferases (HATs)?

They catalyze the transfer of acetyl groups to histones. Signup and view all the answers

What is the function of bromodomains in gene regulation?

They bind to acetylated lysine residues on histones. Signup and view all the answers

What role do co-activators play in gene transcription?

They are recruited to the promoter region by transcription activators to increase gene expression. Signup and view all the answers

Which of the following is associated with gene activation?

Histone acetylation by HATs. Signup and view all the answers

Which of the following best describes the function of the core promoter?

It serves as the binding site for RNA Pol II and basal transcription factors. Signup and view all the answers

What is the distinction between enhancers and silencers in the context of gene regulation?

Enhancers increase the activity of the promoter, while silencers inhibit the activity of the promoter. Signup and view all the answers

How do histone deacetylases (HDACs) impact gene transcription?

They remove acetyl groups from histones, leading to chromatin condensation. Signup and view all the answers

Which of these molecules are directly involved in bringing enhancer/silencer regions in close proximity to the promoter?

Cohesins and condensins. Signup and view all the answers

How do transcription factors, co-activators, and basal transcription factors interplay to activate gene transcription?

Specific transcription factors bound at enhancers attract co-activators to the promoter region, where basal factors and RNA pol II are recruited. Signup and view all the answers

What is the primary role of tissue-specific transcription factors?

To control gene expression patterns unique to different tissue and cell types Signup and view all the answers

How does enhancer activity typically vary between different tissues or cell types?

An enhancer can be active in some tissues/cells and inactive in others. Signup and view all the answers

What is the importance of different sets of transcription factors in the differentiation of lung epithelial cells?

They ensure that each type of lung epithelial cell adopts a unique fate and function. Signup and view all the answers

How do histone modifications contribute to tissue-specific enhancer activity?

Histone modifications can either activate or inactivate enhancers depending on the cellular context. Signup and view all the answers

In lung fibroblasts, how does histone deacetylase influence enhancer activity?

It maintains low histone acetylation, causing inactive enhancer status. Signup and view all the answers

How does histone acetyltransferase influence enhancer activity in hepatocytes?

It promotes histone acetylation, leading to open chromatin and active enhancers. Signup and view all the answers

In the provided example, how do silencers and enhancers regulate Gene X in lung fibroblasts and hepatocytes?

The silencer is inactive and the enhancer active in lung fibroblasts and inactive in hepatocytes. Signup and view all the answers

What is a key difference between the behaviour of silencers in lung fibroblasts compared to hepatocytes, as presented in this information?

Silencers are inactive in lung fibroblasts and active in hepatocytes. Signup and view all the answers

Study Notes

Gene Expression & Regulation

Gene expression is controlled in time and space.
Every cell has the same DNA, but different genes need to be "on" and "off" in different cell types.
Gene expression is regulated for different tissues and cells during development.
Gene expression is regulated at different levels.
- Short term - cells react to external factors.
- Long term - tissue/cell type identity is passed to daughter cells during cell division.
Gene expression is regulated at different levels.
- Epigenetic/Chromatin remodelling
- Transcriptional
- Post-transcriptional
- Translational

Lecture Objectives

Understanding the basic structure and types of transcription factors and their role in transcriptional regulation.
Understanding the role of regulatory DNA sequences in gene transcription regulation.
Understanding the role of histone acetylation and chromatin remodelling in gene transcription regulation.
Understanding the importance and basic principles of tissue-specific regulation of gene transcription.

Transcription Initiation

RNA Pol II binds to a non-coding DNA sequence immediately before the target gene (core promoter).
RNA Pol II is guided to the core promoter by transcription factors (TF).
RNA Pol II and transcription factors form the pre-initiation complex.
RNA Pol II phosphorylation at RBP1 (a protein) starts the process of transcription.

Transcription Elongation

RNA Pol II unwinds the DNA into two strands.
RNA Pol II moves along the DNA, using one strand as a template.
RNA Polymerase II synthesizes a complementary RNA sequence.
The strand used as a template can vary depending on the promoter location.
RNA Pol II adds nucleotides to the 3' end of the growing RNA molecule.

Transcription Termination

RNA Pol II encounters a termination signal and stops the process.
The termination signal is an AAUAAA hexamer in the newly formed mRNA.
RNA Pol II and the mRNA are released.
A new cycle of transcription starts.

Transcription Factors

Transcription factors are proteins that bind to specific DNA sequences and regulate gene transcription (activate or inhibit).
Most factors do not work alone and recruit co-activators to activate gene transcription, or co-repressors to inhibit.

Transcription Factor Domains

Transcription factors have structural domains, functional units, that allow particular interaction—with DNA or other proteins.
They typically have:
- DNA-binding domain (for all TFs)
- Trans-activation/trans-repression domain (for all factors), which has binding sites for co-activators/co-repressors
- Ligand-binding domain (some TFs), e.g. hormone receptors that require ligand binding for activity.
- Dimerisation domain (some factors), e.g. some transcription factors need to form dimers before binding to DNA.

DNA Binding Domain

DNA binding domain allows binding to the major groove of the DNA molecule.
Amino acid sequence in the DNA-binding domain determines specific DNA sequences for binding.
DNA sequences are usually short—6-12 base pairs—and they are transcription factor binding motifs.
E.g. TATA Binding Protein (TBP) binds to TATAAAA and similar short sequences.

Basic and Specific Transcription factors

Transcription factors are either:
- Basic: found in all cells and tissues and help recruit RNA polymerase II to the gene promoter
- Specific: show tissue specificity; regulate gene transcription by acting as activators or repressors.

Core Promoter

The core promoter is located immediately upstream (before) the gene in a fixed position.
The sequence includes the transcription start site (+1).
It contains binding sites for basal transcription factors—basal transcription factors recruit RNA polymerase II to gene.
It is essential for gene transcription.

Enhancers/Silencers

Enhancers/Silencers are regions of non-coding DNA and can regulate nearby genes.
They can be located upstream (before) or downstream (after) the gene promoter.
Enhancers/Silencers are often located far from the gene promoter (sometimes megabases away)
They contain binding motifs for specific transcription factors.
They regulate the activity of the core promoter.

Co-activators

Transcription activators on enhancer elements activate gene transcription by bringing co-activators to the gene promoter.
Co-activators increase gene transcription:
- Opening chromatin (euchromatin) allows RNA Pol II binding.
- Recruiting RNA Pol II and basal transcription factors to the target gene promoter

Co-repressors

Transcription repressors on silencer elements inhibit gene transcription.
Co-repressors induce chromatin condensation by:
- Recruiting co-repressors.
- Binding to DNA and blocking RNA Pol II recruitment

Histone Modification and Chromatin Remodeling

Nucleosomes obstruct gene transcription by preventing transcription complexes from accessing the promoters.
Chromatin remodeling and histone modification are used to “open up” chromatin.
- Nucleosome displacement—ATP-dependent chromatin remodelling enzymes move nucleosomes.
- Chromatin unravelling—histone modifications (acetylation) disrupt DNA/histone interaction

Histones

Histones are highly conserved proteins with positive charges, rich in lysine and arginine.
Histones have an N-terminal tail that contains sites for covalent modifications.
Interactions between positively charged histones and negatively charged DNA are important for gene regulation.

Histone Acetylation

Histone acetyltransferases (HATs) add acetyl groups to lysine residues on histones.
This reduces the positive charge of histones and loosens their interactions with DNA, promoting transcriptional access for gene expression.
Histone deacetylases (HDACs) remove acetyl groups, increasing the positive charge on histones, which then tightly bind to DNA, reducing transcription.
Bromodomains in proteins can recognize and bind to acetylated histones, assisting in gene activation.

Tissue-Specific Regulation

Every cell has the same genes, but different genes need to be "on" and "off"; this depends on the cell type and tissue type.
Long-term, tissue-specific gene expression facilitates growth and development.
Basal transcription factors are found throughout all tissues/cells.
Core promoters are usually active in all cells and tissues.
Specific transcription factors are tissue/cell type specific.
Activator/repressor activity in enhancers/silencers can differ among tissues and thus regulate the activity of genes in a selective manner.

Cell Type-Specific Transcription Factors

Differentiation of each cell requires a specific set of transcription factors.
These factors enable the proper expression of genes required for the cell’s specialized functions

Tissue-Specific Enhancer Activity

Histone modifications can activate or inactivate enhancers in different cells or tissues (e.g. lung fibroblasts and hepatocytes).
Activating enhancers generally require histone acetyltransferases and a generally open chromatin environment.
Inactivating enhancers generally require histone deacetylases and condensed chromatin.

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Description

Test your knowledge on the mechanisms of gene regulation and expression. This quiz covers the roles of transcription factors, DNA regulatory sequences, and the processes involved in both short-term and long-term gene regulation. Perfect for students studying genetics or molecular biology.