Epigenetics 3-4

Question 1

what are the three epigenetic mechanisms?

Answer 1

1) chemical modifications of DNA
2) Post Translation Modifications of Histone Tails
3) Histone variants

Question 2

Explain what IGF2 gene does?

Answer 2

Insulin-like growth factor 2
- matches placental nutrient supply to fetal demand
- Altered IGF2 expression is related to FGR

Question 3

describe the pathway for maternal and paternal IGF2

Answer 3

Maternal:
Insulator binds maternal unmethylated ICR1
H19 gene expressed
Blocks IGF2 expression

Paternal:
Methylation at ICR1 prevents CTCF binding
IGF2 is expressed

Question 4

what is beckwidth-wiedemann syndrome?

Answer 4

gain of methylation of IC1 on the maternal chromosome

Question 5

what did an invitro culture by Market-Velker et al. 2010 show?

Answer 5

• reduced methylation in in vitro cultured blastocysts
• altered gene expression in trophoblast cells = H19> IGF2

Question 6

when was the first IVF baby

Answer 6

1981

Question 7

what effects can ART / IVF have?

Answer 7

• risk of imprinting disorders increased 3.5 fold
• may have increased risk of cardiovascular disease (due to unimprinted genes)

Question 8

Placental specific IGF-II is a major modulator of placental and fetal growth give an example of an experiment that shows this?

Answer 8

Constancia M, Hemberger M, Hughes J et al.
- mouse fetuses in which the Igf2 gene has been completely deleted weigh = 60% of wild-type fetuses

Therefore deletion of the Igf2 gene transcript (P0) specifically expressed in the placenta leads to FGR.

Question 9

Experiment involving placental-specific IGF II showed?

Answer 9

• Placental amino acid transport is initially upregulated
• later the compensation fails = fetal growth restriction
  experimental evidence shows:
• imprinted gene action in the placenta directly controls supply of maternal nutrients to the fetus and fetal growth

Question 10

what is chromatin?

Answer 10

a complex of DNA and histone protein in chromosomes

Question 11

describe the nucleosome core particle ?

Answer 11

DNA: ~ 147 base pairs
- wraps 1.67 left-handed super helical turns

Histone Core Octamer:
Histone = Small highly conserved basic protein
102-135 amino acids

Histone N-terminals = histone tails
Extend out of the core nucleosome
Subject to modifications

Question 12

what makes up a histone octamer?

Answer 12

Histone octamer has two copies of each core histone:
H2A, H2B, H3, H4
= 2 H2A-H2B dimers and 1 H3-H4 tetramer

Question 13

what histones effect the chromatin structure when modified mainly?

Answer 13

H3 and H4