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Miscellaneous > MCB Lecture 27 Epigenetic Modifications > Flashcards

MCB Lecture 27 Epigenetic Modifications Flashcards

0
Q

… play a major role in stem cell differentiation

A

Epigenetic modifications

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1
Q

What are the functions of epigenetic modifications?

A
  1. Delineate the chromosome
  2. Package the chromosome
  3. Alter gene expression
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2
Q

What is the definition of an epigenetic modification? (3)

A
  1. Mitotic ally heritable
  2. Change in gene expression without change to DNA sequence
  3. Reprogrammed in gametogenesis
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3
Q

How does epigenetic modification have a role in chromosome structure?

A

Heterochromatin and euchromatic have different epigenetic modifications

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4
Q

What are the two forms of DNA packaging?

Differentiate between the two in terms of gene expression

A

Heterochromatin: dense, genes off
Euchromatin: loose, genes on

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5
Q

Describe the structure of a nucleosome

A

Octamer core of eight subunits (2x H2A H2B H3 H4)
H1 clamp

Histone tails protruding

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6
Q

How do histones form bonds with DNA?

A

Histones have a positive charge due to lysine and arginine.
The DNA is negative

Electrostatic interaction

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7
Q

What are the two categories of epigenetic modification?

A

DNA methylation

Histone tail modification

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8
Q

Describe the effect of DNA methylation

A

Genes are switched off

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9
Q

What does it mean when a gene is unmethylated?

A

Doesn’t necessarily mean that the gene is switched on

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10
Q

How is DNA methylation layed down?

A

De novo methyl transferases

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11
Q

Differentiate between the function of
DNMT1
DNMT3A
DNMT3B

A

DNMT1: maintains methylation after DNA replication

DNMT3A and DNMT3B: lay down methylation

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12
Q

Describe what happens to DNA methylation at DNA replication

A

One strand of the new double helix will have the original methylation

DNMT1 lays down methylation of the complimentary strand

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13
Q

When is DNA methylation layed down?

A

In early development

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14
Q

Describe the features of ICF syndrome

A

Immunodeficiency Chromosomal and Facial abnormalities

There is a mutation in the gene for DNMT3B
Thus, methylation is not layed down
Hypo methylation

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15
Q

How does ICF syndrome arise?

A

Mutation in the gene for DNMT3B

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16
Q

In ICF there is hypomethylation of … (4)

A
  1. Immune genes
  2. The inactive X chromosome
  3. Centromere
  4. Patterning
17
Q

What are histone tail modifications?

A

The histone tails that protrude from nucleosomes undergo epigenetic modification

18
Q

Which molecules lay down histone tail modifications?

What else can these molecules do to chromatin?

A
  1. Histone Methyltransferases
    HMTs
  2. Chromatin proteins

They remove or modify the modifications

19
Q

What are the two types of histone modification?

A

Acetylation

Methylation

20
Q

Describe the effect of acetylation on histone tails

A

Activation of the gene

21
Q

What is the histone code?

A

Since where are many histone tails and there are many different modifications, the histone code is the overall effect of the histone tail modifications

22
Q

How does histone acetylation work?

A

Acetylation of the tail leads to a decrease in the positive charge of the histone. It thus has reduced affinity for the DNA

23
Q

What is the function of histone methylation?

A

Either activation or inhibition

24
Q

What are the two histone methylations that result in inactivity?

A

H3K9me

H3K27me

25
Q

What is the histone methylation that results in increased activity?

A

H3K4me

26
Q

Differentiate between H3K9me and H3K27me

A

H3K9me : constitutive

H3K27me : facultative

27
Q

How do the histone tail modifications affect chromatin packing?

A

The modifications act as a docking site for other chromatin proteins
These other proteins recruit factors that alter the structure of chromatin

28
Q

What are some proteins that read histone tail modifications and bring about changes in chromatin structure?

A

CHD1
HP1
CBX2

29
Q

How does CHD1 work?

What is it?

A

It unpacks chromatin

It is a chromatin protein

30
Q

What does HP1 do?

What is it?

A

It recruits DNMT1

It is a chromatin protein

31
Q

What does CBX2 do?

What is it?

A

It brings about other epigenetic modifications

It is a chromatin protein

32
Q

What are long non-coding RNAs?

Give an example

A

These are RNAs that have been spliced, capped and tailed

They associate with RNA and bring about change in chromatin structure and gene expression

XIST

33
Q

What are the mechanisms of Long Noncoding RNA function?

A

They bind to regions of DNA, recruit proteins and act as:

Guide
Scaffold
Decoys
Signal
Enhancer
34
Q

Describe the function of XIST long noncoding RNA

A

This RNA is synthesised, and binds to the DNA on the chromosome from which it was synthesised.

Once bound, it forms a loop with which proteins bind.
These proteins are histone methyl transferases PRCL

These proteins add methylation to the histone tails of this chromosome

35
Q

What are the hall marks of a Barr body? (4)

A
  1. Low acetylation
  2. CgP island methylation
  3. H3K9me and H3K27me
  4. Long non coding RNA
36
Q

Describe the mechanism of X inactivation

A

During development in the foetus (at gastrulation), each cell randomly inactivates on of the X chromosomes

This is so that each cell only produces only lot of X chromosome product (dosage compensation)

From then on, the same chromosome will be inactive in that cell and all its progeny

There is only one gene on the inactivate chromosome that is active: the XIST gene. It codes for a long noncoding RNA that coats that chromosome and recruits protein that increases the methylation of the histone tails

37
Q

Describe how Barr bodies are a manifestation of epigenetic silencing (2)

A

They are a silent pocket at he periphery of the cell

They have no RNA pol activity

38
Q

What is Rett syndrome?

What does the mutation lead to?

A

Rett syndrome is a x-linked neurodevelopmental disorder.

The mutation is a mutation in MECP2 which is a methyl binding domain protein

39
Q

Describe the phenotype of Rett syndrome in females

A

Variable.
Heterozygous females can have very severity of phenotype because they may have 95% of the mutant X chromosome inactivates

Due to mosaicism

40
Q

On a molecular level, where is methylation, and when does is it normally present?

A
  1. On the guanine on CpG islands of DNA - normally unmethylated
  2. Intergenic regions - normally silenced
  3. Repetitive elements - normally silenced
41
Q

Methylation of the repetitive elements and intergenic regions corresponds to …

A

The integrity of the genome

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