Lecture 17b

Question 1

When is the Agouti gene more highly expressed / overexpressed?

Answer 1

When the ERV is in euchromatin.

Question 2

What does the ERV near the Agouti gene function as?

Answer 2

Either an enhancer or as a second promotor (we’re not sure which).

Question 3

What does the Agouti gene produce?

Answer 3

A yellow stripe in black fur.

Question 4

When the Agouti gene is overexpressed, what are these mice more prone to?

Answer 4

Diabetes and obesity.

Question 5

What is a Pseudoagouti coat?

Answer 5

Looks agouti but there are some yellow hairs in the fur.

Question 6

What is Pleiotropy?

Answer 6

Range of coat color and weight in completely inbred Avy mice.

Question 7

What determines the extent of fur color in mice with the Avy locus?

Answer 7

The percent of cells in which the ERV is in heterochromatin determines fur color.

Question 8

What do the offspring of pseudoagouti parents look like?

Answer 8

Generally, pseudoagouti parents had more pseudoagouti offspring including pups and grand-pups.

Question 9

What do the offspring of yellow/orange-looking parents look like?

Answer 9

Generally, they appear as yellow/orange-looking offspring in pups and grand-pups.

Question 10

What does the similar appearance of parent to offspring in the mice with the Agouti gene show?

Answer 10

This showed epigenetic inheritance of the methylation state of the ERV element.

However, the epigenetic inheritance is NOT 100%, it depends on the mouse.

Question 11

What does Folate form?

Answer 11

Folic acid and vitamin B9

Question 12

Why is Folate important for DNA methylation?

Answer 12

A folate pathway indirectly provides the methyl for DNA and protein methylation.

Question 13

What is one way to increase DNA methylation?

Answer 13

Having a high folate diet.

Question 14

Why are Folic acid supplements important for pregnant women to take?

Answer 14

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.

Question 15

In the Avy mice, what did increasing their folate intake do?

Answer 15

Caused a higher proportion of offspring to have the Agouti fur color (due to more heterochromatin).

Question 16

If the heterochromatin is 70% and euchromatin is 30%, what fur color can we expect?

Answer 16

Pseudoagouti

Question 17

If the heterochromatin is 40% and euchromatin is 60%, what fur color can we expect?

Answer 17

An intermediate fur color

Question 18

If the heterochromatin is 5% and euchromatin is 95%, what fur color can we expect?

Answer 18

Yellow/orange fur due to overexpression of Agouti gene.

Question 19

T/F: Effects of having higher folate in the diet are only inherited to pups and not to grand-pups.

Answer 19

False! It is inherited to both pups and grandpups (F2) of mcie.

Question 20

When the Avy mice were exposed to alcohol, what occurred?

Answer 20

Exposure to alcohol caused a higher proportion of offspring to have the Agouti fur color.

Alcohol was related to more DNA methylation.

Question 21

When we use electron microscopy, what does heterochromatin appear as?

Answer 21

It can be seen as darkly-staining regions in the interphase nucleus.

Question 22

Where is the heterochromatin localized in a cell?

Answer 22

Localized to the periphery of the nucleus and around the nucleolus.

It moves back and forth between these areas.

Question 23

What does a large proportion of heterochromatin associate with? Where is this at?

Answer 23

A large proportion of heterochromatin associates with the nuclear lamina proteins that are at the nuclear periphery.

Question 24

T/F: As we age and grow older, the amount of heterochromatin increases.

Answer 24

False! As people get older, more of their peripheral heterochromatin gets lost.

Question 25

What is Hutchinson-Gilford progeria? What causes this?

Answer 25

This is a condition in which individuals age 10X faster than normal.

This is due to a mutation in the lamin A.

Question 26

As we get older, who wins out in controlling the genome: heterochromatin or euchromatin?

Answer 26

Euchromatin wins out because there is less heterochromatin as we age.

Question 27

Is the loss of heterochromatin with age slowed by alcohol consumption?

Answer 27

It seems like it but not everybody agrees so it is controversial.

Question 28

Describe the fur color of each.

Answer 28

Top: Pseudoagouti
Middle: Intermediate
Bottom: Yellow/orange (overexpression of Agouti gene)

Question 29

What are the arrows pointing at?

Answer 29

Top arrow is the heterochromatin at the periphery of the nucleus. Bottom arrow is the nuclear lamina proteins.

Question 30

Compare the images and explain what is happening.

Answer 30

The left has heterochromatin. The right has barely any to no heterochromatin so this indicates an aging disease.

Question 31

Younger or older?

Answer 31

Younger, there is lots of heterochromatin

Question 32

Younger or older?

Answer 32

Older, there is fewer heterochromatin.