11. Epigenetics and DNA Methylation Basics

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Questions and Answers

What percentage of CpG regions in the genome are heavily methylated?

40-60%

20-40%

80-100%

60-80% (correct)

What is the primary function of CpG islands in relation to gene expression?

To bind RNA polymerase directly

To act as enhancer regions

To act as gene promoter ‘traffic lights’ (correct)

To prevent gene transcription entirely

Which of the following techniques is used to directly quantify the percentage of cytosine in DNA samples?

Gel electrophoresis

Enzyme-linked immunosorbent assay (ELISA)

Bisulfite sequencing (correct)

PCR amplification

In which context is global DNA methylation particularly useful?

As a potential biomarker for psychiatric disorders (A) Signup and view all the answers

Which of the following is a limitation of measuring DNA methylation?

Low sensitivity of bisulfite sequencing (A) Signup and view all the answers

What happens to unmethylated cytosines during bisulfite sequencing?

They are converted to uracil (C) Signup and view all the answers

How does hypermethylation affect tumor suppressor genes in cancer?

Inactivates them (C) Signup and view all the answers

What type of samples are considered to have low accessibility yet high invasiveness?

Brain and heart (A) Signup and view all the answers

What is a major concern regarding the correlation between epigenetic findings and disease?

Accessibility of tissue samples can bias findings (D) Signup and view all the answers

What is the role of RNA polymerase in relation to DNA methylation?

It is prevented from binding by DNA methylation (B) Signup and view all the answers

What is the primary role of micro RNAs (miRNAs) in gene expression?

To downregulate expression of mRNAs (C) Signup and view all the answers

Which technique is used to measure histone modifications?

Chromatin immunoprecipitation (ChIP) (C) Signup and view all the answers

Which of the following statements about DNA methylation is true?

It represses gene transcription. (C) Signup and view all the answers

What is a characteristic feature of miRNAs?

They are single-stranded and 21-23 nucleotides long. (B) Signup and view all the answers

What condition is directly associated with the expansion in the Huntingtin (HTT) gene?

Huntington’s disease (B) Signup and view all the answers

What does the term 'epigenetics' refer to?

Stable and heritable changes to gene expression without altering the DNA (C) Signup and view all the answers

What is the significance of Waddington's 'epigenetic landscape'?

It describes the differentiation of pluripotent stem cells (A) Signup and view all the answers

How can environmental factors influence disease risk?

Through gene x environment interactions (B) Signup and view all the answers

Which of the following statements about twins is true?

Twins can have different disease outcomes despite identical genetic material. (D) Signup and view all the answers

What is 'epigenomics' focused on?

Analyzing the complete set of epigenetic alterations (C) Signup and view all the answers

Why might XX females not express certain genes compared to XY males?

As a result of hormonal differences affecting gene regulation (B) Signup and view all the answers

What is the role of the 'epigenetic code'?

To maintain different phenotypes in various cell types (B) Signup and view all the answers

What role do histones play in the structure of chromatin?

They allow DNA to be condensed. (C) Signup and view all the answers

What determines the openness or availability of DNA in chromatin?

The tightness of packing around histones. (C) Signup and view all the answers

Which of the following statements about nucleosomes is true?

Nucleosomes are made of histone proteins and DNA. (C) Signup and view all the answers

What is the basic structure of DNA before it is packaged into chromatin?

Naked DNA. (C) Signup and view all the answers

Which of the following correctly describes euchromatin?

It is loosely packed and more accessible. (C) Signup and view all the answers

What components form the core octamer of a nucleosome?

H2A, H2B, H3, H4. (D) Signup and view all the answers

What is the function of the H1 monomer in nucleosomes?

It increases the tightness of nucleosome packing. (A) Signup and view all the answers

In gene expression, what factor is not a key consideration?

Availability of nucleotides. (B) Signup and view all the answers

How many base pairs approximately wrap around each histone octamer in a nucleosome?

146 bp (C) Signup and view all the answers

What is the role of histone acetyltransferases (HAT)?

They add acetyl groups to histones. (A) Signup and view all the answers

Which histone modification is indicated by H3K27me2?

Histone H3 with di-methylation at position 27. (B) Signup and view all the answers

What effect does histone deacetylases (HDAC) have on chromatin?

It condenses chromatin by removing acetyl groups. (C) Signup and view all the answers

What type of modification does phosphorylation refer to in histones?

Adding a phosphate group to serine. (C) Signup and view all the answers

What distinguishes global methylation from gene-specific methylation?

Gene-specific methylation has no effect on global methylation. (D) Signup and view all the answers

Which amino acid is primarily associated with acetylation in histones?

Lysine (D) Signup and view all the answers

Which of the following is NOT a post-translational modification of histones?

Glycosylation (A) Signup and view all the answers

What general function does methylation serve in histone modification?

It can alter gene expression by compacting chromatin. (C) Signup and view all the answers

How is the nomenclature for histone modifications typically structured?

By identifying the histone type followed by modification details. (B) Signup and view all the answers

What is a consequence of histone acetylation?

Enhanced transcriptional activity. (A) Signup and view all the answers

Study Notes

Epigenetics - XY3121

Epigenetics is the study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence. It modifies how genes are read, not the genes themselves.
Epigenetic modifications include DNA methylation and histone modifications. DNA methylation primarily affects gene expression, while histone modifications impact gene accessibility.
A crucial concept in epigenetics is the interplay between genetic and environmental factors. The environment can affect how genes are expressed.

Lecture Aims

Define and describe: epigenetics, epigenetic modifications, the mechanistic link between epigenetics, disease risk.
Explain molecular basis: of epigenetic modifications (DNA methylation, histone modifications).
Describe measurement and limitations: of epigenetic modifications.
Associate epigenetic modifications: with disease pathophysiology and treatment development.

What is Epigenetics? - Part 1

The discussion centres on cellular function, location, DNA content, RNA expression, and protein expression. The note suggests that these factors differ between various cell types with similar genetic makeup.

What is Epigenetics? - Part 2

The "nature vs. nurture" discussion is expanded, emphasizing the interaction between genetics and environmental factors in determining a person's susceptibility to diseases.

What is Epigenetics? - Part 3

The question is explored of why identical twins who possess identical genes can have different disease risks and why XX and XY individuals have different levels of gene expression despite the same genetic constitution.

What is Epigenetics? - Part 4

The nature vs. nurture argument is expanded upon, discussing the combined effects of genetic traits and environmental conditions in establishing disease risks.

What is Epigenetics? - Part 5 (Definitions)

Epi: Prefix meaning "over," "above," or "outer."
Epigenetics: Heritable changes in gene expression occurring without DNA sequence alterations.
Epigenomics: The study of the complete set of epigenetic alterations.
Epigenetic code: The combination of epigenetic features impacting cellular phenotypes.

Gene Expression - Part 1

Gene expression determines cellular function after mRNA translation.
The prompt questions molecular factors which affect gene expression and why cardiomyocytes do not express proteins needed for synaptic function.

Gene Expression - Part 2

The detailed diagram of transcription and translation is presented. The process illustrates how a gene's information is converted to a protein.

Chromatin Structure - Part 1

DNA has several structural levels. It begins as "naked DNA," wrapped around histone proteins to form nucleosomes. DNA availability (a factor impacting gene expression) is determined by how tightly DNA wraps around the histones, which can vary between euchromatin and heterochromatin sections of the genome.

Chromatin Structure - Part 2 (Histones)

Histones are highly conserved proteins which allow DNA condensation and organisation. This structure is critical for how tightly DNA is packaged, therefore dictating gene access and cellular function.

Chromatin Structure - Part 3 (Histones)

Here, the structure of nucleosomes and histones, especially their role in DNA packaging, is displayed in detail.

Chromatin Structure - Part 4 (Chromatin)

The tightness of DNA packing determines the "openness" or "availability" of DNA—in heterochromatin (tight) compared to euchromatin (loose)--with implications for gene expression. The fundamental question is how this correlates with enzyme action related to transcription.

Chromatin Structure - Part 5 (Chromatin)

The importance of epigenetic modifications and their relation to determining the accessibility of DNA and subsequent mRNA transcription.

DNA Methylation - Part 1

DNA methylation is a chemical modification to the DNA molecule.
Methylation does not alter the DNA sequence; rather, it changes how genes are expressed.

DNA Methylation - Part 2 (Where)

Methylation commonly occurs, in the genome. A CpG dinucleotide (cytosine and guanine next to each other) serves as a primary site for methylation.

DNA Methylation - Part 3 (Where)

CpG islands (CpG-rich regions of the genome), are important because they frequently lie near gene promoters. They control gene expression to regulate cellular function.

DNA Methylation - Part 4 (Where)

The overall composition of the genome shows that 60-80% of CpG sites are heavily methylated.

DNA Methylation - Part 5 (What it does)

Methylation inhibits mRNA transcription by physically preventing RNA polymerase binding to DNA.

DNA Methylation - Part 6 (How it's measured)

Enzyme-linked immunosorbent assays (ELISAs) and bisulfite sequencing are used to measure DNA methylation.

DNA Methylation - Part 7 (Why it matters)

Global DNA methylation patterns can function as indicators of particular biological conditions and/or diseases, such as ADHD or bipolar disorder comorbidities, due to altered phenotypic clusters.
DNA methylation patterns are also important for gene-specific considerations, particularly related to cancer.

DNA Methylation - Part 8 (Limitations)

A fundamental limitation of epigenetic analysis using any method is the "cell-type specificity" of epigenetic modifications.
The ability to access various tissue samples for analysis can be restricted based on the complexity and invasiveness.

DNA Methylation - Part 9 (Limitations)

The differences between global DNA methylation and gene-specific methylation.

Histone Modifications - Part 1

Histones, proteins that wrap DNA, can also be modified, altering their interaction with DNA and impacting gene expression.

Histone Modifications - Part 2 (Nomenclature)

A detailed nomenclature for histone modifications exists to ensure precise and unambiguous description of these chemical changes to histone proteins.

Histone Modifications - Part 3 (How they're made)

Histone acetyltransferases (HATs) add acetyl groups to lysine residues to relax chromatin structure. Histone deacetylases (HDACs) remove these acetyl groups to condense chromatin structure

Histone Modifications - Part 4 (What they do)

Precise roles for histone modifications in relation to gene expression are more complicated to identify compared to simple effects. Histone modifications act as signaling mechanisms that control gene expression.

Histone Modifications - Part 5 (How they are measured)

ChIP (Chromatin Immunoprecipitation) is a technique that can be used to analyze histone modifications. Formaldehyde cross-linking, fragmentation, immunopurification, de-crosslinking, and purification steps lead to determining the locations of histone modifications using techniques like dot blot, PCR, and sequencing

MicroRNAs (miRNAs) - Part 1

MicroRNAs are small, non-coding RNA molecules that regulate gene expression through complementary interactions with target mRNAs.

MicroRNAs (miRNAs) - Part 2

The biogenesis of miRNAs is described.

MicroRNAs (miRNAs) - Part 3

miRNAs act as important elements in cellular regulatory mechanisms, regulating gene expression. These molecules exhibit a complex interplay with the environment via mRNA expression to help adjust for external stimuli.

MicroRNAs (miRNAs) - Part 4 (Clinical Implications)

miRNAs can serve as potential therapeutic targets.

Parent-of-Origin Effects - Part 1

In mammals, most genes are expressed from both parental copies (biallelic).

Parent-of-Origin Effects - Part 2 (Clinical Case PWS)

Prader-Willi syndrome, caused by genetic defects, often affects the nutritional/gastrointestinal systems and involves neurological implications which are a result of gene loss.

Parent-of-Origin Effects - Part 3 (Clinical Case AS)

Angelman Syndrome, a neurodevelopmental disorder. The syndrome arises from a deficiency in maternally-expressed genes.

Parent-of-Origin Effects - Part 4 (Clinical Cases)

A comparison of Prader-Willi and Angelman syndromes clarifies the concept of parent-of-origin effects. The important feature is that inheritance from the maternal or paternal copy affects gene expression, and gene loss/defect correlates with phenotypic consequences.

Introduction to Epigenetics - Video (Part 2)

A video summary concerning epigenetics and its significance in biology.

Wider Reading & Viewing - Nessa Carey PhD

The importance of reading and viewing the materials presented by Nessa Carey, PhD is emphasized.

Activity - Global DNA Methylation

Determining the limitations of methodologies used for measuring global DNA methylation; one example uses ELISA in rat brain tissue.

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Description

This quiz explores key concepts in epigenetics, focusing on DNA methylation and its implications for gene expression and cancer. Test your understanding of CpG regions, global DNA methylation, and the techniques used to analyze these modifications.