Epigenetic phenomena

Question 1

What are the two ways in which DNA expression can be changed without changing the sequence?

Answer 1

Methylation/demethylation of DNA regions

Histone modifications

Question 2

True or false: you can pass on epigenetic changes

Answer 2

True

Question 3

What is epigenetics?

Answer 3

The study of stable, heritable changes that do not involve DNA changes

Question 4

How is epigenetic information stored?

Answer 4

On the chromatin in the form of a methylation pattern of Cytosine bases

Question 5

What three items does the cell need to maintain the correct interpretation of epigenetic information?

Answer 5

Writers
Copiers
Readers

Question 6

What is the function of writers in epigenetic information?

Answer 6

Enzymes that methylation cytosine bases in response to signals

Question 7

What is the function of copiers in epigenetic information

Answer 7

Enzymes that copy a methylation pattern from an old DNA strand to a new one

Question 8

What is the function of readers in epigenetic information?

Answer 8

Enzymes that recognize methylated stretches of DNA and initiate silencing of the affected chromosomal regions

Question 9

What are the three major regions of DNA that are silenced by methylation?

Answer 9

1. highly repetitive DNA
2. Telomeres
3. Centromeres

Question 10

Where are CpG regions usually found?

Answer 10

On the 5’ end of genes

Question 11

True or false: methylation of CpG region has no effect on the surrounding DNA regions

Answer 11

False–they are also silenced

Question 12

What is the action of DNMT3a and DNMT3b?

Answer 12

methylation of DNA (they are methyltrnsferases)

Question 13

What is the enzyme that methylates the newly synthesized strand of DNA?

Answer 13

DNMT1

Question 14

Why is DNA methylation useful for the repair machinery of the cell?

Answer 14

Can identify new/old strand based on methylation

Question 15

What is the function of MBPs (methylcytosine binding proteins)?

Answer 15

Repress transcription of methylated DNA regions

Question 16

What is Rett syndrome?

Answer 16

X-linked dominant disorder that is a defect in methyl-CpG binding proteins (failure to maintain chromatin silencing). This is perinatally lethal in boys

Question 17

What are the four types of modification of histones?

Answer 17

Acetylation
Methylation
Phosphorylation
Ubiquitination

Question 18

What is H2Az?

Answer 18

A variant of the histone H2A. CAn be exchanged for H2A to increase the transcription of silenced regions

Question 19

Once a deacetylated region of histones has been established, what are the next three steps to spread the deacetylation/inactivation?

Answer 19

1. Methylate the histones
2. Methylated histones bind to HP1 proteins
3. HP1 proteins bind histone methylases.

Question 20

Histone modification takes place on what end of the polypeptide, the N or C terminus?

Answer 20

N-terminus

Question 21

True or false: all of the four type of histone modifications can take place on a histone all at once

Answer 21

True

Question 22

What are boundary elements?

Answer 22

Chromatin barriers where methylation stops

Question 23

Why does the self propagating nature of DNA inactivation present a problem when chromosomal aberrations occur?

Answer 23

Because the silencing aspect of the transferred region can spread to part of the newly attached chromosome that should not be silenced

Question 24

What is imprinting?

Answer 24

DNA silencing in a call that causes it to identify itself specifically, as well as whether it is paternal or maternal

Question 25

How does imprinting occur?

Answer 25

DNA methylation and acetylation based on the imprinting center of each chromosome

Question 26

A female will reprogram her gamete chromosomes to make them look like paternal or maternal chromosomes?

Answer 26

Maternal

Question 27

A male will reprogram his gamete chromosomes to make them look like paternal or maternal chromosomes?

Answer 27

Paternal

Question 28

How does the X chromosome become inactivated?

Answer 28

The XIST region on the X chromosome to be inactivated is trancribed, and the RNA recruits methyltransferases

Question 29

True or false: all of the genes on the inactivated X chromosome are methylated/deactivated?

Answer 29

False-- a few areas are not

Question 30

True or false: phenotypes of a mutation can vary, depending on whether it is on the maternal or paternal chromosome?

Answer 30

True

Question 31

What is uniparental dismony?

Answer 31

The condition where a person has only maternally or only paternally imprinted chromosomes

Question 32

What is beckwith-Wiedemann syndrome?

Answer 32

When a child inherits both homologues of a portion of chromosome 11, resulting in overabundance of insulin-like growth factor 2 (leads to severe hyperglycemia)

Question 33

There is a deletion of chromosome 15 on the PATERNAL chromosome. What is the disease? Symptoms?

Answer 33

Prader-Willi syndrome--obesity, food seeking behavior, MR

Question 34

There is a deletion of chromosome 15 on the MATERNAL chromosome. What is the disease? Symptoms?

Answer 34

Angelman syndrome--unusual facial features, SZs, MR

Question 35

How does hypermethylation cause CA?

Answer 35

Silencing a tumor suppressor gene

Question 36

How does hypomethylation cause CA?

Answer 36

1. Genomic instability leading to breakage and resealing double stranded breaks. This can change oncogenes or tumor suppressor genes 2. Increase mutations in a CA already present

Question 37

What is systemic lupus erythematosus?

Answer 37

an autoimmune disease where T cells genome is hypomethylated, and leads to the expression of silenced, endogenous retroviruses

Question 38

What are the two classes of drugs that can be used to influence DNA methylation?

Answer 38

1. Histone deacetylase inhibitors | 2. DNA methyltransferase inhibitors (5-azacytidine)

Question 39

What is 5-azacytidine used for?

Answer 39

Inhibits DMNT to reverse hypermethylation of tumor suppressor genes found in acute myeloid leukemia.

Question 40

What is Rett syndrome?

Answer 40

X-linked dominant mutation in a MBP (MEP2), that leads to autism-like symptoms. (if in boys=death)

Question 41

Once a deacetylated region of histones has been established, what happens next?

Answer 41

1. Histones become methylated 2. Methylated histones bind to HP1 proteins 3. HP1 proteins bind to histone methyltransferases, propagating the effect

Question 42

What is the cause for Lupus?

Answer 42

Hypomethylated T cell genes, and inactivation of DMNT1. This leads to the expression of endogenous retroviruses

Question 43

HDAC inhibitiors do what to the genome? What is this used in?

Answer 43

promotes expression of silienced genes in chronic lymphocytic leukemia

Question 44

How can hypermethylation be reversed?

Answer 44

DNMT inhibitor aza-cytidine

Question 45

How can excessive chromatin silencing be reversed?

Answer 45

HDAC inhibitors