Epigenetic Regulation of Gene Expression

Question 1

Where is DNA methylated

Answer 1

on the 5 position of cytosine

Question 2

What is the enzyme and donor for DNA methylation

Answer 2

DNMT - enzyme

SAM - donor

Question 3

What are the requirement of a CpG island

Answer 3

over 60% G+C content
CpG:GpC >0,6 ration
>200bp

Question 4

What are the 2 methods of demethylation

Answer 4

TET genes

Active process using TDG

Question 5

How do TET genes demethylate DNA

Answer 5

modifies methylcysteine to hydroxymethylcytosine –> this a poor substrate for DNMT1 and methylation is lost upon cell divison

Question 6

How does repair mediated processes demethylate DNA

Answer 6

Use the TDG enzyme which removes a base in base-excision repair

Question 7

What is the DNMT for maintenace

Answer 7

DNMT1

Question 8

What are the de novo DNMTs

Answer 8

DNMTs3a/3b

Question 9

What are the effects of knockouts of each DNMT

Answer 9

DNMT1 % 3a/b –> embyronically lethal

DNMTL –> involved in genomic imprinting hence get biallelic expression from normally parentalyl imprinted genes

Question 10

How does DNA methylation cause a repressive chromatin structure

Answer 10

Methylated DNA binds MBP and rectuirs HACs

Question 11

What is the state of CTCF in maternal chromomsomes

Answer 11

Locus is not methylated hence CTCF can bind and therefore igf2 does not have access to the enhance

Question 12

What are the active histone methylations

Answer 12

H3K4

Question 13

What are the repressive histone methylations

Answer 13

H3K9 , H3K27

Question 14

How doe histone methylations recurit DNMt

Answer 14

HP-1 proteins can attract DNMTs

Question 15

Name some biological functions of epigenetically silencing genes

Answer 15

X-inactivation
Inativation of parasitic sequences
Genomic imprinting

Question 16

what are the parental origins of a mule and hinney

Answer 16

Mule - male donkey, female horse

Hinney - male horse, female donkey

Question 17

what do yo uget if you get LOI and LOH at the 11p15 locus in somatic cells

Answer 17

Wilms Tumour

Question 18

what do yo uget if you get LOI and LOH at the 11p15 locus in germline cells

Answer 18

Overgrowth BWS

Question 19

What occurs if you get H19 DMR hypomethylation –> meaning that h19 is overexpressed

Answer 19

Russel silver syndrome

growth retardation

Question 20

What are the 2 theories of imprinting

Answer 20

Haig

Barlow –<> methylation is a defence against foreign DNa

Question 21

What specific histone methyltransferase inactivaates oct4

Answer 21

G9a –> induces H3K9me2 and recruits DNMT hence inactivating Oct4 allowing for differentiation

Question 22

Deletion in prada willi syndorme

Answer 22

15q11 deletion –> loss of paternal expression of genes –> mainly due to paternal deletion

Question 23

What are the symptoms of prada-willi syndrome

Answer 23

Poor suckling, hyperphagia, obesity, developmental delay

Question 24

What are the symptoms of BWS

Answer 24

Big body: macrosomia
Big tonigue: macroglossia
Big abdomen: Omphacele
Big organs: visceromegaly
Getting bigger: can get tumorus e.g. Wilms and NB

Question 25

How many clusters of imprinted genes have we identified so far

Answer 25

13

Question 26

Describe a gene that doesnt show predominant expression from a maternal or paternal allel

Answer 26

Grb10 Maternally expressed in embryogenesis However paternally expressed in adults and can regulate social behaviour

Question 27

Descrbie the 2 methods throguh whcih ICR work

Answer 27

LncRNAs | Insulator model

Question 28

What is the link between imprinting and adiposity

Answer 28

Gnas mutations --> can lead to severe obseity not due to hyperphagia

Question 29

Mutation of what imprinted gene can affect neonatal feeding

Answer 29

Loss of Magel2 imprinted gene (normally paternally expressed) Interestingly also get low oxytocin in the hypothalamus --> potential to give an oxytocin shot at birth to correct this

Question 30

Defects in imprinting genes can affect sleep in what conditions

Answer 30

Angelmanns | Prade Willi

Question 31

What are the 2 theories of imprinting

Answer 31

Haig | Barlow

Question 32

WHere does less CpG depletion occur

Answer 32

At CpG islands --> may be because these remain unmethylated in the germ line

Question 33

What can increases the activtiy of TET genes

Answer 33

Vitamin C

Question 34

What domain containing proteins can recogenise methylated CGs and may contributed to methylated mediated repression

Answer 34

MBD-containing proteins | Although may be redundant as deletion does not lead to reactivation of genes

Question 35

What domain containing proteins can recorgnise unmethylated CpGs

Answer 35

CXXC

Question 36

TET2 mutations are linked to what disease

Answer 36

TET2

Question 37

What is a commonly mutated gene releated to methylation in AML

Answer 37

DNMT3a --> one of the most commonly mutated genes in AML