MCB Lecture 27 Epigenetic Modifications

Question 0

… play a major role in stem cell differentiation

Answer 0

Epigenetic modifications

Question 1

What are the functions of epigenetic modifications?

Answer 1

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

Question 2

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

Answer 2

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

Question 3

How does epigenetic modification have a role in chromosome structure?

Answer 3

Heterochromatin and euchromatic have different epigenetic modifications

Question 4

What are the two forms of DNA packaging?

Differentiate between the two in terms of gene expression

Answer 4

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

Question 5

Describe the structure of a nucleosome

Answer 5

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

Histone tails protruding

Question 6

How do histones form bonds with DNA?

Answer 6

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

Electrostatic interaction

Question 7

What are the two categories of epigenetic modification?

Answer 7

DNA methylation

Histone tail modification

Question 8

Describe the effect of DNA methylation

Answer 8

Genes are switched off

Question 9

What does it mean when a gene is unmethylated?

Answer 9

Doesn’t necessarily mean that the gene is switched on

Question 10

How is DNA methylation layed down?

Answer 10

De novo methyl transferases

Question 11

Differentiate between the function of
DNMT1
DNMT3A
DNMT3B

Answer 11

DNMT1: maintains methylation after DNA replication

DNMT3A and DNMT3B: lay down methylation

Question 12

Describe what happens to DNA methylation at DNA replication

Answer 12

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

DNMT1 lays down methylation of the complimentary strand

Question 13

When is DNA methylation layed down?

Answer 13

In early development

Question 14

Describe the features of ICF syndrome

Answer 14

Immunodeficiency Chromosomal and Facial abnormalities

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

Question 15

How does ICF syndrome arise?

Answer 15

Mutation in the gene for DNMT3B

Question 16

In ICF there is hypomethylation of … (4)

Answer 16

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

Question 17

What are histone tail modifications?

Answer 17

The histone tails that protrude from nucleosomes undergo epigenetic modification

Question 18

Which molecules lay down histone tail modifications?

What else can these molecules do to chromatin?

Answer 18

1. Histone Methyltransferases
   HMTs
2. Chromatin proteins

They remove or modify the modifications

Question 19

What are the two types of histone modification?

Answer 19

Acetylation

Methylation

Question 20

Describe the effect of acetylation on histone tails

Answer 20

Activation of the gene

Question 21

What is the histone code?

Answer 21

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

Question 22

How does histone acetylation work?

Answer 22

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

Question 23

What is the function of histone methylation?

Answer 23

Either activation or inhibition

Question 24

What are the two histone methylations that result in inactivity?

Answer 24

H3K9me | H3K27me

Question 25

What is the histone methylation that results in increased activity?

Answer 25

H3K4me

Question 26

Differentiate between H3K9me and H3K27me

Answer 26

H3K9me : constitutive | H3K27me : facultative

Question 27

How do the histone tail modifications affect chromatin packing?

Answer 27

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

Question 28

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

Answer 28

CHD1 HP1 CBX2

Question 29

How does CHD1 work? | What is it?

Answer 29

It unpacks chromatin | It is a chromatin protein

Question 30

What does HP1 do? | What is it?

Answer 30

It recruits DNMT1 | It is a chromatin protein

Question 31

What does CBX2 do? | What is it?

Answer 31

It brings about other epigenetic modifications | It is a chromatin protein

Question 32

What are long non-coding RNAs? Give an example

Answer 32

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

Question 33

What are the mechanisms of Long Noncoding RNA function?

Answer 33

They bind to regions of DNA, recruit proteins and act as: ``` Guide Scaffold Decoys Signal Enhancer ```

Question 34

Describe the function of XIST long noncoding RNA

Answer 34

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

Question 35

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

Answer 35

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

Question 36

Describe the mechanism of X inactivation

Answer 36

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

Question 37

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

Answer 37

They are a silent pocket at he periphery of the cell They have no RNA pol activity

Question 38

What is Rett syndrome? | What does the mutation lead to?

Answer 38

Rett syndrome is a x-linked neurodevelopmental disorder. | The mutation is a mutation in MECP2 which is a methyl binding domain protein

Question 39

Describe the phenotype of Rett syndrome in females

Answer 39

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

Question 40

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

Answer 40

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

Question 41

Methylation of the repetitive elements and intergenic regions corresponds to ...

Answer 41

The integrity of the genome