Epigenetics & Imprinted Genes in Early Development

Question 1

Why have scientists not be able to succeed in parthenogenesis (formation of either gynogenetic or androgenetic diploid)?

Answer 1

Growth of the fetus is regulated by both parental genomes inherited from the sperm and egg.

Question 2

What is a CpG island?

Answer 2

Stretches of alternating cytosines and guanines in DNA which are targets for methylation during genomic imprinting.

Question 3

During nuclear transfer experiments, what relationship was found between maternal genome vs. paternal genome and the developing embryo?

Answer 3

1. Maternal-only = large embryo, small placenta.

2. Paternal-only = small embryo, large placenta.

Question 4

When was the first example of an imprinted gene discovered and what was the gene?

Answer 4

1. 1991

2. Insulin-like Growth Factor-2 (IGF-2) in mice

Question 5

How many imprinted genes have been discovered to-date in mice and humans?

Answer 5

~80

Question 6

Give three examples of imprinted genes.

Answer 6

1. IGF-2
2. IGF2r
3. H19

Question 7

What are three important things to know about IGF-2?

Answer 7

1. Found on chromosome 7 in mice and 11 in humans.
2. In humans and mammals, the PATERNAL IGF-2 i expressed (maternal is imprinted).
3. If both alleles are expressed it can lead to kidney tumor (called Wilms’ cancer).

Question 8

What are three important things to know about IGF2r?

Answer 8

1. Receptor for IGF-2.
2. Found on chromosome 17 in mice and 6 in humans.
3. In mice the MATERNAL gene is expressed (paternal is silent).

Question 9

What are three important things to know about H19?

Answer 9

1. Found on chromosome 7 in mice and 11 in humans.
2. Maternally expressed (paternal imprinting) and its mRNA isn’t translated.
3. Plays a role in transcriptional regulation, tumor suppression, and oncogenesis.

Question 10

What are four important things to know about XIST?

Answer 10

1. It’s the gene on the X chromosome which codes for RNA to convert the second X in a female to become an inactive Barr body.
2. NOT a random process, therefore NOT an example of imprinting.
3. Paternal X coding for amnion, placenta, umbilical cord also inactivated.

Question 11

What are six characteristics of imprinted genes?

Answer 11

1. DNA methylation
2. CpG-rich regions
3. Physically linked in clusters with other imprinted genes (~80%)
4. Histone modification (acetylation, methylation), called the “Histone code.”
5. Genetic imprinting control elements are discovered in the gene clusters, which are needed for the regional control of imprinting or imprinted gene expression.
6. Multiple cis-acting sequences

Question 12

What are the four steps of the life cycle of methylated imprinted genes?

Answer 12

1. Maintenance - Maintaining imprints while chromosomes duplicate and divide after fertilization.
2. Erasure - By embryonic day 12-13, demethylation of imprinted genes occur.
3. Establishment - After erasure, de novo methylation starts again in both parental gene lines and continues after birth (different pathways for gametes of each gender)
4. Reading - Conversion of methylation or chromosomal imprints into differential gene expressions.

Question 13

Contrast maternal vs. paternal imprinting during preimplantation development.

Answer 13

Maternal = passive methylation
Paternal = active demethylation