Test 3 Epigenetics

Question 1

Basics of Epigenetics

Answer 1

Heritable changes in gene expression that occur without change to DNA sequence.

• Reversible
• Heritable environmental induction
• Paternal genome reset at fertilization
• Maternal genome reset gradually.

Question 2

The 3 main epigenetic mechanisms?

Answer 2

• DNA methylation
  
  • DNA methyltransferases ( - )
• Histone Modification
  
  • Histone deacetylases ( - )
  • Histone acetylases ( + )
    
    • Acetylation relaxes genome so that transcription can occur.
  • Histone methyltransferases ( - )
  • Methyl - binding domain protein. MECP2
• RNA mediated epigenetic regulation
  
  • Small RNAs
  • Long non-coding RNAs, lncRNA
  • Usually involved in facilitating DNA methylation or Histone modification.

Question 3

Epigenetic influences?

Answer 3

Epigenetic imprinting and X-Chromosome inactivation

Question 4

Role of DNMT3?

Answer 4

• De novo methylation of cytosine
  
  • Occurs during gametogenesis

Question 5

Role of DNMT1?

Answer 5

• Most common
• Responsible for maintaining methylation during replication.
  
  • Adds them to the newly synthesized strands.

Question 6

When does cytosine methylation usually occur?

Answer 6

When cytosine is followed by a guanine.

Question 7

Enzyme responsible for DNA demethylation?

Answer 7

TET

Question 8

Role of methylation?

Answer 8

Surpresses downstream regions.

Question 9

Describe Histone Modification

Answer 9

• Covalent mods to Histone proteins, specifically how tightly the nucleosomes are packed.
  
  • Tightly packed chromatin is not avaliable for gene expression
• ​

Question 10

Heterochromatin

Answer 10

Nucleosomes are tightly packed together, highley enriched with 5-methylcytosine.

Question 11

Euchromatin?

Answer 11

Less tightly packed allowing binding of RNA polymerase and regulatory proteins.

Question 12

Once histone marks are set do they pass down to future daughter cells? If so what is the implication?

Answer 12

• Yes they are passed down
• This is why you cannot remake your entire body by using the DNA from a nose cell.
  
  • It has already epigenetically differentiated.

Question 13

Explain RNA - mediated Epigenetic regulation

Answer 13

• Small RNAs recruit proteins to transcript, that in turn recruit modifying enzymes.
• Long RNAs act as scaffolds for RNA-binding proteins.
  
  • Chromatin modifying complexes

Question 14

Two cycles heavily influenced by histone modification?

Answer 14

Circadian rhythm and menstrual cycle.

Question 15

Example of long lasting effects of Epigenetic markers

Answer 15

Kids born to mothers during the Dutch famine winter, had a higher chance for diabetes and other metabolic diseases.

Theses markers were set during the pregnancy.

Question 16

Explain X-Chromosome inactivation

Answer 16

• In homochromatic (XX) individuals
  
  • Placental mammals - random X inactivation per cell.
    
    • One is completely inactivated
      
      • Females are chimeric due to different Xs being inactivated throughout body.
  • Marsupials: imprinted X inactivation
    
    • X that gets shut off is from one parent.

Question 17

3 systems of epigenetics in mammals

Answer 17

Heterochromatin maintenance

Developmental controls

Tissue specific expression controls.

Question 18

What is imprinting?

Answer 18

Parent of origen dependent monoallelic DNA methylation or inactivation.

Question 19

What is Xist?

Answer 19

• Xist is found on the non silenced X chromosome and
• Recruits: histone modifications and DNA methylations

Question 20

What is Tsix?

Answer 20

Is the anti-sense gene of Xist, it blocks Xist on its own chromosome and upregulates Xist on the other chromosome.

Question 21

What amino acids is commonly acetylated in Histone modification?

Answer 21

Lysine (K)

Question 22

Epigenetic Mechanism of Disease:

Rett Syndrome

Answer 22

• Methyl CpG binding protein
• Generally de novo ​mutation
  
  • Patients dont live long enough to have kids.
• Disease largely only seen in females, since males with this die in the womb.

Question 23

Epigenetic Mechanism of Disease:

MTHFR

Methyl-ene-tetrahydro-folate reductase

Answer 23

• Linked to altered patterns of DNA methylation
  
  • Increased risk for breast and colorectal cancer.
• Also effects reaction to medication.

Question 24

Epigenetic Mechanism of Disease:

Give an example of Imprinting Disorder

Answer 24

• Two syndromes are located on the same chromosome (15) but which syndrome that occurs depends on if it came from the mother or father.
  
  • Angelman syndrome: Maternal LOF
  • Prader-Willi- syndrome - Paternal LOF
• Beckwith-weidemann syndrome:
  
  • Activation of lgf2 on maternal chromosome 11
    
    • Gene is not silenced in the female, causing prenatal and post-natal overgrowth.
      *

Question 25

Example of a disease due to defects in Histone modifiation

Answer 25

Coffin-Lowry Syndrome

Profound intellectual deficiencies

Question 26

Example of defect in methylation

Answer 26

Fragile X syndrome

Caused by CGG repeat in FMR1

Question 27

What is an oncogene? and how does DNA methylation play a role with cancer?>

Answer 27

• Gene responsible for cell growth
  
  • Hypomethylation : removing histones activates these genes causing cells to proliferate.
  • Hypermethylation: Increased suppression of Tumor suppressor genes results in tumor growth, causing cancer.

Question 28

How are epigenetic marks detected?

Answer 28

• Bisulfate sequencing
  
  • If C is methylated then they stay Cs
  • If they are unmethyled the Cs become Us and then Ts.