The Epigenome

Question 1

What is the genome?

Answer 1

• The complete set of genetic material in a cell

- The DNA sequence that is present in a single full set of chromosomes

Question 2

What is the nucleosome?

Answer 2

Histone proteins and DNA forming the first level of packaging?

Question 3

What is chromatin?

Answer 3

Is the combination of histones with DNA

Question 4

What are the two types of chromatin?

Answer 4

Euchromatin
-Gene rich
Heterochromatin
-Gene poor

Question 5

What is the packing solution?

Answer 5

• Nucleosomes are wound up to form 30nm fibres
• Fibres are then wound up further with scaffold proteins to generate high order structure
• Chromosomes are the most densely packed form of genomic DNA

Question 6

What is the epigenome?

Answer 6

• Sum of all heritable changes in the genome that do not occur in the primary DNA sequence and that affect gene expression
• In other words, a change in the phenotype but not the genotype

Question 7

Examples of epigenetic mechanisms

Answer 7

• DNA methylation
• Histone modification
• X inactivation
• Genomic imprinting

Question 8

What is DNA methylation?

Answer 8

Is the addition of a methyl group in the 5’ position of a cytosine

Question 9

What is DNA methylation catalysed by?

Answer 9

Catalysed by the DNA methyltransferase enzyme

Question 10

What does DNA methylation require in order for the methyl group to be provided?

Answer 10

Requires S-adenosyl methionine to provide the methyl group

Question 11

Where does DNA methylation in differentiated cells occur?

Answer 11

In differentiated cells, it occurs in CpG di-nucleotides

Question 12

What catalyses DNA demethylation?

Answer 12

TET enzymes catalyse DNA demethylation

Question 13

What are the effects on gene expression by DNA methylation?

Answer 13

-Turns transcription off by preventing the binding of transcription factors

Question 14

What is histone modification?

Answer 14

Is the addition of chemical groups to the proteins that make up the nucleosome

Question 15

How are modifications named in histone modification?

Answer 15

Named based on the histone, the amino acid and the actual modification

Question 16

What are the 3 classes of enzymes that bind to histone tails?

Answer 16

• Writers
• Erasers
• Readers

Question 17

What do writer enzymes do and give examples?

Answer 17

Writers-Enzymes that add histone modification
Examples:
-Histone acetyltransferase
-Histone methyltransferase

Question 18

What do eraser enzymes do and give examples?

Answer 18

Erasers-Enzymes that remove histone modification
Examples:
-Histone deacetylase
-Histone demethylase

Question 19

What do reader enzymes do and give examples?

Answer 19

Readers-Enzymes that bind to the modification and alter gene activity
Examples:
-Bromodomain and extra terminal proteins
-Chromodomain proteins

Question 20

What are the roles of histone modification?

Answer 20

Can repress or activate transcription depending on where it occurs

Question 21

What does acetylation at Lysine residue do?

Answer 21

Acetylation at Lysine residue relaxes the chromatin structure and makes it accessible for transcription factors

Question 22

How can histone modification occur and what can their effects do?

Answer 22

Can occur concurrently and so their effects can interact or modify each other

Question 23

What is X-inactivation?

Answer 23

Is the inactivation of one of the 2 X chromosome in every somatic cell in females

Question 24

What does X-inactivation ensure?

Answer 24

Ensures that every somatic cell in all humans has the same number of active copies of every gene

Question 25

What is the process of X inactivation?

Answer 25

1. The Xist gene is transcribed as a long non-coding RNA from the x-inactivation centre and binds all over the X chromosome
2. Histone acetylation is removed and DNA and histone methylation occurs
3. Inactive X chromosomes is heterochromatic

Question 26

How is one X chromosome still kept active during X inactivation?

Answer 26

Tsix is derived by transcription in the opposite direction and antagonises Xist RNA to keep one X active

Question 27

What is genomic imprinting?

Answer 27

Is the selective expression of genes related to the parental origin of the gene copy

Question 28

How are imprinted genes found?

Answer 28

Tend to be found in clusters

Question 29

How is genomic imprinting mediated?

Answer 29

Is mediated by imprinting control regions

Question 30

What is the process of genomic imprinting and what are essential to the process?

Answer 30

• One copy is silenced by DNA methylation, catalysed DMNT3a and histone methylation leading to inactivation
• LNcRNAs are essential to the process

Question 31

What happens to imprinting patterns during gamete formation?

Answer 31

Imprinting patterns are reset during gamete formation