Lecture originally designed by Phoebe Lu
Epigenetics and Development
Our Goals:
- To build our own definition of “epigenetics”;
- To classify the major mechanisms of chromatin remodeling;
- To investigate how external environment/behaviour can trigger a completely different
developmental fate
- To propose, and interpret some experiments that allow us to shed light on this
phenomenon (in a specific case)
1. What could be the underlying mechanism driving the different developmental trajectory of the
organisms studied in today’s class?
- It is possible that diet plays a significant role in the differences observed between Queen
bees and worker bees. It is known that Queen bees are fed ‘royal jelly’ where as worker bees
are fed a diet composed of less nutritionally dense components. These dietary differences
might contribute to differences in signally pathways, hormone levels, or gene expression
patterns that ultimately lead to the phenotypic differences observed between Queen and
worker bees.
2. a) With one or two partners, take two minutes to come up with a definition of “epigenetics”:
- Gene regulation occurring outside of the DNA sequence
- Heritable
- Inheritance of a phenotype
b) After listening to other classmates’ ideas, provide a more complete (if necessary) definition
of “epigenetics”:
- Epigenetics refers to the inheritance of a phenotype not explained by the organism’s specific
sequence of DNA
3. a) What are different mechanisms that can affect developmental trajectory, and that could be
affected/directed by an “outside factor”?
-
Structure of DNA/chromatin
Presence of different gradients established externally
Lecture originally designed by Phoebe Lu
b) What are the mechanisms that can affect chromatin structure?
-
Coiling & Supercoiling
Acetylation/ Methylation
Histone Modifications
Methylases
Factors involved with mitosis
Chromatin remodeling structures: differences between nucleosomes
4. What would you predict about gene expression patterns in the two distinct developmental
trajectories if epigenetics is driving the phenotype?
-
Differential expression of growth genes
Differential expression of reproductive genes
Pheromone expression differences
Differences in overall energy distribution
5. Researchers (Grozinger et al., 2007) actually checked… what do you notice about the gene
expression patterns in individuals following each of the two developmental trajectories?
-
This study showed an upregulation of genes associated with foraging behavior in worker
bees
Further, an upregulation of genes associated with reproducation and longevity was found
in Queen bees
6. What kind of protein/factor could be a key component of the epigenetic control of
developmental trajectories? How would you test your hypothesis?
-
As seen above, differential gene expression patterns lead to the differential phenotypes
observed between Queen bees and Worker bees
We know that a dietary difference is associated with whether a bee becomes Queen or a
worker
It is therefore likely that a protein/substance contained in royal jelly alters the global gene
expression patterns in bees
Knowing DNA methylation patterns and chromatin structure are large players in epigenetic
differences, perhaps a protein altering DNA methylation patterns is present in royal jelly
You could test this hypothesis by isolating removing proteins associated with DNA
methylation from royal jelly and see if the removal of such factors are sufficient to prevent
bees from becoming phenotypically ‘Queen.’ (This assumes known DNA methylation
associated proteins are found in royal jelly)
Lecture originally designed by Phoebe Lu
7. What did Kucharski and colleagues find, and what does their experiment suggest?
-
Kucharski found that bee larvae injected with Dnmt3 siRNA, to create Dnmt3 knockdowns,
were found much more likely to develop into Queen-like bees.
This suggests that wild type Queen bees have lower Dnmt3 expression
Further, this suggests that a property of royal jelly might directly/indirectly alter Dnmt3
expression
8. a) What component of the food in question is most likely to affect gene regulation?
- Since none of the major royal jelly proteins seem associated with methylation, perhaps it is a
lipid found in royal jelly that affects Dnmt3 expression?
b) How does the food in question activate a transcriptionally silenced gene?
-
A study by Spannhoff et al (2011), showed that the active component of royal jelly is
10HDA, a lipid.
Further, studies exposing cells to just 10HDA was sufficient in activating a previously
transcriptionally inactive gene, Fas.
This showed that 10HDA is capable of activating gene expression, perhaps leading to the
inactivation of Dnmt3.