Epigenetics Flashcards

1
Q

What is meant by epigenetics

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2
Q

What are the main epigenetic tools

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3
Q

What is the structure and function of a histone*

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There are four main types of core histones: H2A, H2B, H3, and H4. Each nucleosome core consists of an octamer made up of two copies of each core histone (H2A, H2B, H3, and H4), forming a disk-like structure.
Nucleosome Assembly: The DNA wraps around this histone octamer approximately 1.65 times, covering around 147 base pairs of DNA in each nucleosome.

Each histone protein has flexible N-terminal tails that extend outward from the nucleosome core. These tails are rich in lysine and arginine, making them positively charged and able to interact with negatively charged DNA.
The histone tails are accessible for post-translational modifications, such as methylation, acetylation, phosphorylation, and ubiquitination, which affect chromatin structure and gene regulation.

H1 is a fifth type of histone that binds to the DNA as it exits the nucleosome, helping to stabilize the nucleosome structure and promote further compaction into higher-order chromatin structures.

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4
Q

How are histones covalently modified*

A

Histone methylation can occur on lysine or arginine residues

Methylation of histones can either activate or repress transcription, depending on which residue is modified and the number of methyl groups added (mono-, di-, or tri-methylation).

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5
Q

What is the difference between heterochromatin and euchromatin in terms of histone modification *

A

Histones in euchromatin regions are typically highly acetylated, particularly on lysine residues in the histone tails. Acetylation neutralizes the positive charge of lysines, loosening the interaction between histones and negatively charged DNA. This creates a more open, accessible chromatin structure, facilitating transcription.

In heterochromatin, histones are generally hypoacetylated (low acetylation levels). Without acetylation, the positive charges on histone tails are retained, allowing stronger binding between histones and DNA, leading to a more compact, closed structure that is transcriptionally silent.

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6
Q

What are the two types of repressed chromatin

A

Constitutive heterochromatin
Facultative heterochromatin

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7
Q

What is meant by Constitutive Heterochromatin*

A

refers to chromatin that is permanently in a condensed, transcriptionally inactive state

Constitutive heterochromatin is marked by specific histone modifications that maintain a repressive, compact state. Key modifications include tri-methylation of histone H3 on lysine 9 (H3K9me3), which serves as a binding site for heterochromatin protein 1 (HP1), a protein that promotes chromatin condensation.

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8
Q

What is meant by Facultative Heterochromatin*

A

facultative heterochromatin is reversible and dynamic, allowing it to be transcriptionally active or inactive at different times or in different cell types

One classic example of facultative heterochromatin is X-chromosome inactivation

Facultative heterochromatin is marked by specific histone modifications associated with gene repression but can change to accommodate reactivation. A key modification is H3K27 trimethylation (H3K27me3), which is catalyzed by the Polycomb repressive complex 2 (PRC2). H3K27me3 is recognized by Polycomb repressive complex 1 (PRC1), which helps maintain the chromatin in a compacted state.

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9
Q

What is H3K27 methylation and how is it deposited *

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10
Q

What is the link between epigenetics and cancer

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11
Q

What is x inactivation*

A

is a process in female mammals where one of the two X chromosomes in each cell is randomly silenced to ensure that females (XX) and males (XY) have an equal dosage of X-linked genes. This process is crucial because having two active X chromosomes could lead to an overexpression of genes that are critical for cellular functions, which can disrupt cellular and developmental processes.

In each cell of a female embryo, one of the two X chromosomes is randomly chosen to be inactivated. Once an X chromosome is inactivated, all the descendant cells retain that same inactive X chromosome

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12
Q

With the example of a tortoiseshell cat, explain how epigenetics can affect phenotype (is an example of x inactivation)

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13
Q

Explain how epigenetics affects agouti mice

A

They are genetically identical
Difference? The mother of the skinny brown mouse provided with methyl-rich diet for
two weeks before mating, through the pregnancy (about 3 weeks) and lactation

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14
Q

How are twins used to study epigenetics

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15
Q

How does the Dutch famine show how epigenetics can be inherited

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16
Q

What is meant by imprinting

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17
Q

Give an example of a gene in humans is typically imprinted

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18
Q

Name a theory which is likely to explain imprinting

A

Genetic Conflict Hypothesis

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19
Q

Explain the Genetic Conflict Hypothesis

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20
Q

What is the role of epigenetics in plants

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21
Q

What histone methylation binding events determine whether it is repressive or not

A

Methylation of certain lysine residues, such as histone H3 at lysine 9 (H3K9) and histone H3 at lysine 27 (H3K27), is commonly associated with transcriptional repression. These modifications create a binding platform for proteins involved in compacting chromatin and silencing genes.

Methylated histone residues can attract repressor proteins that recognize specific methylation patterns. For instance, the methylation of H3K9 and H3K27 is recognized by chromodomain-containing proteins, such as heterochromatin protein 1 (HP1) and Polycomb repressive complex 2 (PRC2), respectively. These proteins bind to methylated histones and recruit additional factors that help condense chromatin.

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22
Q

Where does DNA methylation occur and how does it repress gene expression

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23
Q

What is DNA methylation facilitated by in mammals

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24
Q

When is DNA hemi-methylated

25
What is the link between DNA methylation and disease
26
What regions does DNA methylation usually occur in
27
Why does DNA methylation occur at intergenic regions
28
What intergenic regions does dna methylation occur at
29
Why are transposable /repetitive elements methylated
30
What is the link between methylation and cancer
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When is DNA methylation erased
32
How is methylation inherited
33
How was dna methylation previously identified
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How is dna methylation now identified
35
How is X inactivation carried out
36
What are long non coding RNA sequences
37
What is Xist
38
What is the key functional part of Xist
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What is the mechanism of Xist
40
What is HOTAIR
41
What is the mechanism of HOTAIR
42
What is the link between long non coding RNAs and disease
43
Give some examples of Long non-coding RNAs that are linked to named diseases
44
What are the two main types of transposons
Retrotransposon DNA transposon
45
What are the characteristics of retrotransposons
46
What are the characteristics of DNA transposons
47
What are the two types of retrotransposons + characteristics
48
Why do transposable elements (TEs) lose their ability to transpose over time
49
Who discovered TEs
50
How are TEs silenced
51
Why do TEs transpose and where should they transpose to survive
52
What is meant by a mutualistic relationship in the context of TEs
53
Name some ways that TEs can become useful to its host
TE derived promoters and enhancers TEs acting as TAD boundaries TE derived lncRNA transposase-transcription factor fusions
54
How can TE derived promoters and enhancers be produced
55
How can TEs act as a TAD boundary
56
How can transposase-transcription factor fusions arise
57
What are the Phenotypic and evolutionary effects of TEs
58
Why do some primates not have tails
59
Give some other examples of TE derived traits