Intro to epigenetics

Question 1

What are epigenetic changes?

Answer 1

heritable changes in genome fxn w/o changing the DNA sequences. Think of them as molecular switches

Question 2

Name three types of epigenetic changes

Answer 2

1. DNA methylation
2. histone modifications (acetylation removes the positive charge of histones, decreasing the strength of its binding to DNA)
3. miRNA

Question 3

What is the role of cpG islands in epigenetic modifications?

Answer 3

1. Islands are located in promoter region and first exon of genes
2. methylation in promoter region and 1st exon of genes
3. cpG islands are predominantly unmethylated in the healthy state

Question 4

Describe the epigenetic changes you would see when a gene is turned on

Answer 4

Unmethylated cytosine and acetylated histones

Question 5

What is the fxn of miRNAs?

Answer 5

normal development, cell cycle regulation and homeostasis. Involved incarcinogenesis

Question 6

What is genomic imprinting?

Answer 6

Imprinted genes are ones where we only inherit a single working copy, either mom or dad’s. The others remain silenced until gametogenesis. Affected by diet

Question 7

Describe 3 diseases where epigenetics leads to carcinogenesis

Answer 7

1. BRCA1==breast cancer
2. RB=retinoblastoma
3. VHL=renal cell carcinoma

Question 8

Describe the mechanism by which cpG hypermethylation enhances cancer risk

Answer 8

1. hypermethylation of tumor suppressors
2. MGMT hypermethylation prevents fxn of DNA repair protein
3. Methylation of guanine converts G:C pair to A:T causing p53 inactivation
4. Methylated MGMT promoter results in increased sensitivity to chemotherapy

Question 9

What is FAP?

Answer 9

familial adenomatous polyposis. Lots of adenomas at a young age.

Question 10

What causes FAP?

Answer 10

Mutation in APC gene

Question 11

What does the APC gene do?

Answer 11

Causes dysplastic crypts and early adenomas. Will accumulate other mutations to become a carcinoma

Question 12

Describe the genetic changes that occur sequentially in colon cancer

Answer 12

1. Inactivation of APC=dysplastic crypt
2. Mutation of KRAS=adenoma
3. p53 inactivation=carcinoma

Question 13

How does APC carry out its function molecularly?

Answer 13

APC binds axin to degrade beta-catenin. When Wnt signal is present, APC cannot operate and wnt genes are transcribed into mRNA

Question 14

What does APC regulate?

Answer 14

1. amount of free beta catenin
2. microtubule assembly
3. AXIN
4. apoptosis pathways

Question 15

What does beta-catenin regulate?

Answer 15

1. Transition of G1-S
2. Anchors cadherin to actin for tight junctions and cell membranes. Normally, differentiated cells lose Wnt signal and that helps to maintain spatial relationship between colonic crypts

Question 16

What histological changes would you see in colon cancer?

Answer 16

1. Abnormal crypt fission
2. increased crypt fission
3. more crypts, and longer crypts with increased branching

With additional mutations, will start to see dysplastic crypts with abnormal branching and diffuse beta catenin expression