Epigenetics

Question 1

What are the four main characteristics of epigenetic phenomena?

Answer 1

1. Different gene expression with an identical genome
2. Inheritance through cell division, even through generations
3. Consistent ON/OFF switch
4. Erasable & reset-able

Question 2

What is the basic principle of Waddington’s epigenetic landscape?

Answer 2

That cell fates are established in development much like a marble rolls down to the point of lowest local elevation

Different cell states = different paths the cell can take

Question 3

What are three specific examples of epigenetic phenomena?

Answer 3

1. Chromatin-mediated gene silencing
2. Centromere marking by the histone variant CENP-A (attachment to spindle during mitosis)
3. Reinforcing feedback loops involving trans-acting factors that have a specific initiation event and are ‘inherited’ in the cytosol during cell division

Question 4

How can DNA methylation be inherited through cell division?

Answer 4

Maintenance methyltransferases propagate epigenetic marks through somatic cell division

Question 5

What are three chemical modifications (to DNA or histones) that can potentially be inherited?

Answer 5

1. Methylation (methyltransferases)
2. Acetylation (i.e. histone deacetylase)
3. Chromatin structure

Question 6

What is a problem for maintaining an epigenetic state?

Answer 6

That DNA replication is semi-conservative so half of the DNA and histones are old and the other half are new

Question 7

What is the specific type of gene that, when aberrant methylated with 5’-MeC, can lead to cancer?

What sort of therapeutic intervention is possible?

Answer 7

TSG (Tumor suppressor genes)

Therapeutic inhibition of DNA methyltransferase and histone deacetylase (to prevent TSG silencing)