Week 2 Epigenetics

Question 1

1. Describe the four main characteristics of epigenetic phenomena.

Answer 1

1. Different gene expression pattern/phenotype, identical genome
2. inheritance through cell division, even through generations
3. like a switch: on/off
4. erasable: therapeutic potential (inter-convertible)

ex: genetically comparable mothers fed slightly different diet can produce very different offspring (for example fi they were given low or high methyl donor ingredients)

Question 2

2. Explain the basic principle of Waddington’s epigenetic landscape.

Answer 2

-more specific cell differentiation
-his visualization started with this ball at the top of a hill with equal potential to roll into different valleys; ball gets stuck in one valley or another
think of those valleys as activation energy in chemistry

can end up in cell state 1 or cell state 2 (go from multipoint stage but then go to a specific state)

flipping switches as a visualization of epigenetic expression pattern

erasure and resetting of methylation pattern of imprinted genes during gametogenesis is essential- embryos with no active copies or two active copies of imprinted genes would be produced at high frequencies

Question 3

3. List three specific examples of epigenetic phenomena.

Answer 3

• Chromatin mediated gene silencing: heterochromatin domains, X-inactivation,imprinting. Bacteriophage lambda repressor mechanism. Feedback loops in certain cancers
• Prions (mad cow disease, Kreutzfeld-Jacob disease)

1) Effects of paternal grandparent diet on grandchildren mortality risk (increased diabetes risk and BMI)

2) Genetically comparable mothers who were fed
slightly different diet (low/high “methyl donor” ingredients) during gestation and nursing produced very different offspring (gene turned off in dark/small mouse. protein regulates color and feeding habits) **large changes to DNA methylation, diet can work at the molecular level

Question 4

4. Describe how DNA methylation can be inherited through cell division.

Answer 4

Maintenance methyltransferases propogate epigenetic marks through somatic cell division

Question 5

5. Name three chemical modifications to DNA or histones that can potentially be inherited.

Answer 5

a

Question 6

6. Describe how epigenetic mechanisms and inheritance can occur both inside and outside the nucleus.

Answer 6

a

Question 7

7. Name a specific type of gene that, when aberrantly methylated with 5meC, can lead to cancer and an approach to therapeutic intervention in this case.

Answer 7

a