Lecture 17b Flashcards
When is the Agouti gene more highly expressed / overexpressed?
When the ERV is in euchromatin.
What does the ERV near the Agouti gene function as?
Either an enhancer or as a second promotor (we’re not sure which).
What does the Agouti gene produce?
A yellow stripe in black fur.
When the Agouti gene is overexpressed, what are these mice more prone to?
Diabetes and obesity.
What is a Pseudoagouti coat?
Looks agouti but there are some yellow hairs in the fur.
What is Pleiotropy?
Range of coat color and weight in completely inbred Avy mice.
What determines the extent of fur color in mice with the Avy locus?
The percent of cells in which the ERV is in heterochromatin determines fur color.
What do the offspring of pseudoagouti parents look like?
Generally, pseudoagouti parents had more pseudoagouti offspring including pups and grand-pups.
What do the offspring of yellow/orange-looking parents look like?
Generally, they appear as yellow/orange-looking offspring in pups and grand-pups.
What does the similar appearance of parent to offspring in the mice with the Agouti gene show?
This showed epigenetic inheritance of the methylation state of the ERV element.
However, the epigenetic inheritance is NOT 100%, it depends on the mouse.
What does Folate form?
Folic acid and vitamin B9
Why is Folate important for DNA methylation?
A folate pathway indirectly provides the methyl for DNA and protein methylation.
What is one way to increase DNA methylation?
Having a high folate diet.
Why are Folic acid supplements important for pregnant women to take?
They prevent neural tube defects (NTD) in the baby.
Low folate levels in early pregnancy are believed to be the cause of more than half of babies born with neural tube defects.
In the Avy mice, what did increasing their folate intake do?
Caused a higher proportion of offspring to have the Agouti fur color (due to more heterochromatin).
If the heterochromatin is 70% and euchromatin is 30%, what fur color can we expect?
Pseudoagouti
If the heterochromatin is 40% and euchromatin is 60%, what fur color can we expect?
An intermediate fur color
If the heterochromatin is 5% and euchromatin is 95%, what fur color can we expect?
Yellow/orange fur due to overexpression of Agouti gene.
T/F: Effects of having higher folate in the diet are only inherited to pups and not to grand-pups.
False! It is inherited to both pups and grandpups (F2) of mcie.
When the Avy mice were exposed to alcohol, what occurred?
Exposure to alcohol caused a higher proportion of offspring to have the Agouti fur color.
Alcohol was related to more DNA methylation.
When we use electron microscopy, what does heterochromatin appear as?
It can be seen as darkly-staining regions in the interphase nucleus.
Where is the heterochromatin localized in a cell?
Localized to the periphery of the nucleus and around the nucleolus.
It moves back and forth between these areas.
What does a large proportion of heterochromatin associate with? Where is this at?
A large proportion of heterochromatin associates with the nuclear lamina proteins that are at the nuclear periphery.
T/F: As we age and grow older, the amount of heterochromatin increases.
False! As people get older, more of their peripheral heterochromatin gets lost.
What is Hutchinson-Gilford progeria? What causes this?
This is a condition in which individuals age 10X faster than normal.
This is due to a mutation in the lamin A.
As we get older, who wins out in controlling the genome: heterochromatin or euchromatin?
Euchromatin wins out because there is less heterochromatin as we age.
Is the loss of heterochromatin with age slowed by alcohol consumption?
It seems like it but not everybody agrees so it is controversial.
Describe the fur color of each.
Top: Pseudoagouti
Middle: Intermediate
Bottom: Yellow/orange (overexpression of Agouti gene)
What are the arrows pointing at?
Top arrow is the heterochromatin at the periphery of the nucleus. Bottom arrow is the nuclear lamina proteins.
Compare the images and explain what is happening.
The left has heterochromatin. The right has barely any to no heterochromatin so this indicates an aging disease.
Younger or older?
Younger, there is lots of heterochromatin
Younger or older?
Older, there is fewer heterochromatin.