epigenetics

Question 1

What is the role of epigenetics

Answer 1

Compartmentalise genes into active and repressed regions by:
- developmental gene expression
- inactivation of X chromosomes
genomic imprinting

Question 2

What is epigenetics predominantly signalled by

Answer 2

Histone modifications and DNA methylation

Question 3

What is the reversibility of epigenetics

Answer 3

• can be duplicated in somatic cell multiplication
• not maintained in germ cells (unlike DNA sequence change)

Question 4

What is X inactivation

Answer 4

-Females have two X chromosomes so one needs to be silenced so genes aren’t over expressed

Question 5

How does X inactivation work

Answer 5

Xist RNA is expressed on one of the X chromosomes which attracts protons required to condense the chromosome.

Question 6

What is genomic imprinting

Answer 6

Non-sequence based inheritance mechanism in which the chemical modification passed on from the mother or father will change the expression or function of gene product

Question 7

What are the ways that methylation repress transcription

Answer 7

• chromatin modification
• compaction of DNA
• blocking binding sites for transcription factors
• methylation of transcription factors

Question 8

What is the ‘5th base’

Answer 8

cytosine can be modified to form 5-methyl cytosine.
It’s presence in DNA can ‘switch-off’ genes

Question 9

What are CpG islands

Answer 9

CpG islands are short stretches of DNA that have a high frequency of the CpG dinucleotide (a cytosine followed by a guanine, linked by a phosphate).

Question 10

How are CpG islands involved in epigenetics

Answer 10

• regulation: at promoters so usually unmethylated so keeps the associated gene active or capable of being activated.
• methylated: often leads to gene silencing.

Question 11

What us a DNA methyl transferase

Answer 11

Enzyme involved in DNA methylation

Question 12

What is the function of DNMT1

Answer 12

• copies existing DNA methylation patterns onto the newly synthesized DNA strand during DNA replication.
• ensures that daughter cells inherit the same methylation

Question 13

What is the function of DNMT3A/B

Answer 13

De novo - forms new methylation patterns on DNA

Question 14

What is the function of DNMT3L

Answer 14

regulatory cofactor for formation of new methylation patterns

Question 15

What does methylation of K27 and K9 do

Answer 15

silences genes

Question 16

What are the effects of cancer on epigenetics

Answer 16

• DNA methylation and histone modification patterns are altered in cancers
• turning off growth inhibitory genes (tumour suppressor genes)
  -turning on growth promoting genes (onco genes)

Question 17

Why is epigenetics important in cancer treatment

Answer 17

• methylation can be used as diagnostic marker and cancer gene identifier
• possible target for therapy
• could reactivate genetically silenced genes

Question 18

What are the consequences of p16 inactivation in cancer

Answer 18

p16 blocks CDK activity
when p16 blocked
increase in inactive pRB by phosphorylation
loss of cellular ability to block cell cycle progression

Question 19

Does p16 inactivation have to be down to epigenetic factors

Answer 19

can also be caused by mutation

Question 20

How does epigenetics contribute to mutations

Answer 20

one allele needs to be silenced for the mutation in the other to be expressed