FTM 64 - Epigenetics and Imprinting

Question 1

When we discuss DNA methylation, what is actually being methylated?

Answer 1

Cytosine is being methylated on its #5 carbon

Question 2

Describe how DNA methylation occurs and how it leads to transcriptional repression.

Answer 2

1. DNA is methylated at cytosine residues by Dnmt3
2. MeCP2 binds to the methyl groups and recruits HDAC1/2
3. HDAC1/2 deacetylates lysine residues of histones, giving them a +ve charge
4. Heterochromatin forms and transcription is repressed

Question 3

Describes how DNA methylation inheritance occurs.

Answer 3

1. When methylated DNA is replicated, the daughter strand is not methyalated. This is referred to as hemimethylated DNA
2. MeCP2 binds to hemimethylated DNA in a different conformation than when it binds methylated DNA. This conformation recruits Dnmt1
3. Dnmt1 will then methylate the other strand of DNA
4. This methylation causes MeCP2 to change conformation, release Dnmt1, and recruit HDAC1/2
5. HDAC1/2 deacetylates the histones causing heterochromatin to form

Question 4

Describe how acetylation and deacetylation affect chromatin

Answer 4

Acetylation neutralizes the positive charge of a histone causing euchromatin to form

Deacetylation replaces the positive charge of the histone causing heterochromatin to form

Question 5

What is ICF syndrome? What causes it?

Answer 5

Question 6

What causes Rett Syndrome? What are its symptoms? When does it present? What population does it primarily affect?

Answer 6

Question 7

How can imprinting make dominant alleles appear recessive and recessive alleles appear dominant?

Answer 7

Question 8

When does imprinting occur?

Answer 8

Gametogenesis

Question 9

What are the symptoms of Prader-Willi and Angelman Syndrome?

Answer 9

Question 10

What are the causes of Prader-Willi and Angelman Syndrome?

Answer 10

Question 11

What is BWS? What causes it? What are its symptoms? What population is at the highest risk for developing BWS and why?

Answer 11

Question 12

How can gel electrophoresis be used to find DNA that has been methylated?

Answer 12

Methylated DNA will not be digested by restricition enzymes so methylated DNA will not run as far as DNA that is unmethylated, after restriction enzyme digestion.

Question 13

What are some drugs that can prevent DNA methylation? How?

Answer 13

Cytidine analogues like Decitabine which cannot be methylated. Additionally, these drugs are known to bind and inhibit DNA methyltransferases.

Question 14

What can Decitabine be used to treat and how does it work?

Answer 14

It is used in Myelodysplastic syndrome & Acute myeloid leukemia. In these disorders the CDKN2B gene (the P15 tumor suppressor gene) is silenced due to a hypermethylated promoter region. The use of Decitabine causes this region to become hypomethylated so that P15 can be expressed and prevent malignant transformation.

Question 15

What are the environmental factors that have been shown to influence or disrupt epigenetic gene silencing and how?

Answer 15

Question 16

As they age, why do MZ twins begin to look more different?

Answer 16

Question 17

How does X-inactivation occur?

Answer 17

DNA methylation and epigenetics

Question 18

Facts to know about Incontenetia pigmenti

Answer 18