Histone Modifications and DNA Methylation

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Questions and Answers

What effect does acetylation of lysines have on DNA?

Inhibits transcription by tightening DNA binding

No effect on transcription or DNA binding

Increases the binding of DNA to histones

Facilitates transcription by loosening DNA binding (correct)

Which enzyme is responsible for the process of DNA methylation?

DNA polymerase

Histone deacetylase

DNA methyltransferase (correct)

RNA polymerase

How does DNA methylation typically affect gene transcription?

It causes transcription to be tissue-specific

It usually has no effect on transcription

It usually enhances transcription

It usually inhibits transcription (correct)

What characterizes CpG islands in vertebrates and plants?

They are typically long and contain many CpG sites Signup and view all the answers

In which context are CpG islands typically unmethylated?

In housekeeping genes Signup and view all the answers

What role do methyl-CpG-binding proteins have in chromatin structure?

They recruit factors that lead to chromatin compaction Signup and view all the answers

What is a characteristic of tissue-specific genes regarding methylation?

They may be silenced by CpG island methylation Signup and view all the answers

Which eukaryotic species are known to have little DNA methylation?

Yeast and Drosophila Signup and view all the answers

What process is responsible for the maintenance of methylation patterns in offspring?

Maintenance methylation Signup and view all the answers

Which component directly binds to enhancers to initiate gene activation?

Regulatory transcription factors Signup and view all the answers

What is the function of a nucleosome-free region (NFR) in eukaryotic genes?

Facilitates transcription initiation Signup and view all the answers

How is de novo methylation characterized in terms of its frequency and regulation?

Infrequent and highly regulated Signup and view all the answers

How do activators function in the context of transcriptional activation?

They recruit coactivators to the promoter Signup and view all the answers

What is the primary role of CpG islands in the genome?

To regulate DNA methylation dynamics Signup and view all the answers

What is the outcome when regulatory transcription factors bind to enhancers?

Activation of gene transcription Signup and view all the answers

Which methylation refers to the initial establishment of methylated sequences in the gametes?

De novo methylation Signup and view all the answers

Which histone variants promote an open chromatin conformation?

H3 variants Signup and view all the answers

What is the primary role of the histone code in gene transcription?

To influence interactions between DNA and histones Signup and view all the answers

Which of the following histone modifications is specifically associated with repression of gene transcription?

Methylation Signup and view all the answers

How does DNA methylation generally affect gene expression?

It typically represses gene expression Signup and view all the answers

What role do CpG islands play in gene expression?

They help initiate transcription when unmethylated Signup and view all the answers

Which of the following statements about histone variants is incorrect?

All histone variants fully replace standard histones in nucleosomes Signup and view all the answers

Which of the following enzymes is primarily responsible for adding acetyl groups to histones?

Histone acetyltransferase Signup and view all the answers

What is one potential consequence of modifications on the amino terminal tails of histones?

They can regulate gene transcription based on their patterns Signup and view all the answers

What is the primary mechanism by which repressors exert their effects on gene expression?

By interacting with corepressors Signup and view all the answers

How can gene repression manifest in a cellular context?

By inhibiting gene activation or long-term silencing Signup and view all the answers

What is a distinct feature of chromatin immunoprecipitation sequencing (ChIP-Seq)?

It maps nucleosome locations within a genome Signup and view all the answers

What structural characteristic is typical of gene regulation in eukaryotes compared to bacteria and archaea?

Eukaryotic genes are usually organized as single genes Signup and view all the answers

What is an effect of heterochromatin formation on gene expression?

Results in long-term gene silencing Signup and view all the answers

In what context is chromatin immunoprecipitation performed?

In species with an entirely sequenced genome Signup and view all the answers

What reinforces the complexity of transcriptional regulation in eukaryotes compared to bacteria?

The functional diversity of regulatory elements like enhancers Signup and view all the answers

Which statement accurately reflects the position of regulatory elements in bacterial gene organization?

Operators are typically located close to the promoter Signup and view all the answers

What are histone variants primarily responsible for in chromatin?

Creating specialized chromatin with distinct functions Signup and view all the answers

How many histone genes are typically found in the human genome?

70 to 80 Signup and view all the answers

Which type of covalent modification is specifically recognized by proteins in the histone code?

Phosphorylation of serine at position 1 in H2A Signup and view all the answers

Which of the following best describes the histone code?

The pattern of modifications that influences chromatin interactions Signup and view all the answers

What is one role of the enzymes that modify histones?

To regulate interactions between DNA and histone proteins Signup and view all the answers

Which histone modification is commonly associated with promoting transcription?

Methylation of histone H3 at lysine 4 Signup and view all the answers

What is one effect of histone modifications on nucleosomes?

They affect how tightly DNA is wrapped around nucleosomes Signup and view all the answers

What common histone modifications are mentioned in regards to nucleosome structure?

Acetylation, methylation, and phosphorylation Signup and view all the answers

What is the main result of glucocorticoid hormone action on gene transcription?

Activation of multiple genes through GREs Signup and view all the answers

Which of the following is NOT a characteristic of CREB protein?

Interacts with GREs Signup and view all the answers

How does CREB protein enhance gene transcription upon activation?

Through interaction with a coactivator after phosphorylation Signup and view all the answers

What is the function of a repressor in gene transcription?

To bind to DNA and inhibit transcription Signup and view all the answers

What is a primary role of glucocorticoids in cell metabolism?

Promoting glucose utilization and fat mobilization Signup and view all the answers

What mechanism is primarily involved in the function of steroid hormone receptors?

Binding and dimerization leading to nuclear entry Signup and view all the answers

What consensus sequence is recognized by CREB protein?

5’-TGACGTCA-3’ Signup and view all the answers

Which type of hormones primarily influences the growth and function of gonads?

Gonadocorticoids Signup and view all the answers

What is the significance of GREs in the context of glucocorticoid action?

They allow activation of many genes through binding Signup and view all the answers

Which of the following statements accurately describes the binding of unphosphorylated CREB?

It can bind to DNA but cannot activate RNA polymerase. Signup and view all the answers

What is the primary function of gene regulation in eukaryotes?

To adapt the level of gene expression according to environmental conditions Signup and view all the answers

Which of the following factors is NOT involved in regulatory mechanisms of gene expression?

RNA polymerase phosphorylation Signup and view all the answers

Which process is primarily responsible for modifying RNA after transcription?

Alternative splicing Signup and view all the answers

What role do small effector molecules play in combinatorial control of gene regulation?

They modulate the activity of transcription factors Signup and view all the answers

Which of the following statements best describes the role of repressor proteins in gene regulation?

They inhibit the transcription of specific genes Signup and view all the answers

How does DNA methylation influence gene expression?

It generally inhibits transcription of associated genes Signup and view all the answers

What best characterizes the combinatorial control of eukaryotic gene regulation?

Concurrent influence of multiple factors including activators and repressors Signup and view all the answers

What is a significant outcome of RNA modification processes in gene expression?

It allows for diverse protein forms from a single gene Signup and view all the answers

What is the role of the sigma (σ) factor in transcription?

It recognizes the core promoter. Signup and view all the answers

Which statement characterizes the function of coactivator complexes?

They alter chromatin structure to influence transcription. Signup and view all the answers

How do activators differ from repressors in their interaction with RNA polymerase?

Repressors inhibit RNA polymerase, while activators facilitate its function. Signup and view all the answers

What is the significance of riboswitches in gene regulation?

They respond to metabolite levels to regulate transcription. Signup and view all the answers

Which of the following roles is NOT associated with transcription factors?

Facilitating DNA replication. Signup and view all the answers

What is a key structural change induced by enhancers in gene regulation?

Forming loops in the DNA to position enhancers near promoters. Signup and view all the answers

In both prokaryotic and eukaryotic systems, which factor is crucial for transcription initiation?

Sigma (σ) factor. Signup and view all the answers

Which statement best describes the interaction of repressors with DNA?

Repressors can sterically inhibit RNA polymerase binding. Signup and view all the answers

Study Notes

### Histone Modifications

Acetylation of lysine residues on histones eliminates the positive charge, making the DNA less tightly bound.
Acetylation facilitates transcription.

DNA Methylation

Covalent attachment of methyl groups (-CH3) to DNA.
Carried out by DNA methyltransferase.
Common in some eukaryotic species, but not all (e.g., yeast and Drosophila have little DNA methylation, while vertebrates and plants have abundant DNA methylation).
In mammals, approximately 2 to 7% of DNA is methylated.
DNA methylation typically inhibits eukaryotic gene transcription.

CpG Islands

Found in vertebrates and plants, near gene promoters.
1,000 to 2,000 nucleotides long and contain a high number of CpG sites.
In housekeeping genes, CpG islands are unmethylated, leading to gene expression in most cell types.
In tissue-specific genes, methylation of CpG islands can silence gene expression.
Methylation may influence the binding of transcription factors.
Methyl-CpG-binding proteins can recruit factors that compact chromatin.

Inheritance of DNA Methylation

Methylated DNA sequences are inherited during cell division.
May explain genomic imprinting, where specific genes are methylated in gametes from either the female or male parent.
The pattern of one copy of the gene being methylated and the other not is maintained in offspring.

### Gene Activation

A series of events leading to gene transcription to produce an RNA molecule.
Requires regulatory transcription factors (activators) binding to enhancers.
Activators recruit coactivators – chromatin remodeling complexes and histone-modifying enzymes – to the promoter region.
An RNA polymerase binds to the core promoter to form a preinitiation complex.
RNA polymerase then elongates the transcript.

### Nucleosome Arrangement

A nucleosome-free region (NFR) exists at the beginning and end of many eukaryotic genes.
Precise positioning of nucleosomes near the beginning and end, but a less regular distribution elsewhere.

Transcriptional Activation

Involves changes in nucleosome position and composition, as well as histone modifications.
Activators recruit chromatin remodeling complexes and histone-modifying enzymes.

Histone Variants

Five types of histone genes, moderately repetitive (H1, H2A, H2B, H3, and H4).
Human genome contains over 70 histone genes.
Most code for standard histones.
Some accumulate mutations, altering the amino acid sequence, creating histone variants.

Histone Variants and Chromatin Structure

Incorporated into a subset of nucleosomes to create specialized chromatin.
Some variants promote an open chromatin conformation, while others promote a closed conformation.
Changes in the composition of histone variants can regulate gene transcription.
Other functions include DNA repair and chromosome segregation.

Histone Code

Over 50 enzymes covalently modify the amino terminal tails of histones.
These modifications affect transcription level by:
- Influencing interactions between DNA and histone proteins.
- Creating patterns that are recognizable by proteins (the histone code).
The histone code provides binding sites for proteins, influencing chromatin structure and ultimately transcription.

Histone Modifications and Structure

Acetylation, methylation and phosphorylation are common histone modifications.
Certain protein codes recognize specific combinations of modifications, such as phosphorylation of serine at position 1 in H2A and acetylation of lysine at the 5th and 8th positions in H4.

Gene Regulation in Eukaryotes

Gene expression is the process of using genetic information to synthesize RNA and proteins, ultimately affecting cell properties and organism phenotypes.
Gene regulation refers to the variable levels of gene expression under different conditions.
The regulation of gene expression is crucial for various biological processes:
- Responding to environmental changes like nutrient availability and stress.
- Generating diverse cell types in multicellular organisms.
- Facilitating developmental changes, as some genes are exclusively expressed during embryonic stages or adulthood.

Levels of Gene Regulation

Transcription:
- Regulatory transcription factors activate or inhibit transcription.
- Nucleosome arrangement and composition influence gene expression.
- DNA methylation can repress transcription.
RNA modification:
- Alternative splicing and RNA editing modify RNA transcripts.
Translation:
- Proteins control translation and mRNA degradation.
- RNA interference regulates gene expression post-transcriptionally.
Post-translation:
- Feedback inhibition and covalent modifications regulate protein activity.

Combinatorial Control of Gene Expression

Most eukaryotic genes are regulated by multiple factors, working in a combinatorial manner.
Factors contributing to combinatorial control:
- Activators stimulate transcription.
- Repressors inhibit transcription.
- Activators and repressors can be modulated by small effector molecules, protein interactions, and covalent modifications.
- Regulatory proteins may alter nucleosome structures near promoters.
- DNA methylation can repress transcription.

Histone Variants and the Histone Code

Histone variants are incorporated into nucleosomes, creating specialized chromatin structures.
Some variants promote open chromatin, facilitating transcription, while others favor closed chromatin, restricting transcription.
The histone code refers to the pattern of covalent modifications on histone tails, influencing DNA-histone interactions and serving as binding sites for proteins that regulate chromatin structure and transcription.