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Enzymes > Epigenetic phenomena > Flashcards

Epigenetic phenomena Flashcards

1
Q

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

A

Methylation/demethylation of DNA regions

Histone modifications

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2
Q

True or false: you can pass on epigenetic changes

A

True

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3
Q

What is epigenetics?

A

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

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4
Q

How is epigenetic information stored?

A

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

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5
Q

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

A

Writers
Copiers
Readers

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6
Q

What is the function of writers in epigenetic information?

A

Enzymes that methylation cytosine bases in response to signals

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7
Q

What is the function of copiers in epigenetic information

A

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

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8
Q

What is the function of readers in epigenetic information?

A

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

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9
Q

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

A
  1. highly repetitive DNA
  2. Telomeres
  3. Centromeres
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10
Q

Where are CpG regions usually found?

A

On the 5’ end of genes

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11
Q

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

A

False–they are also silenced

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12
Q

What is the action of DNMT3a and DNMT3b?

A

methylation of DNA (they are methyltrnsferases)

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13
Q

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

A

DNMT1

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14
Q

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

A

Can identify new/old strand based on methylation

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15
Q

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

A

Repress transcription of methylated DNA regions

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16
Q

What is Rett syndrome?

A

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

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17
Q

What are the four types of modification of histones?

A

Acetylation
Methylation
Phosphorylation
Ubiquitination

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18
Q

What is H2Az?

A

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

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19
Q

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

A
  1. Methylate the histones
  2. Methylated histones bind to HP1 proteins
  3. HP1 proteins bind histone methylases.
20
Q

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

A

N-terminus

21
Q

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

A

True

22
Q

What are boundary elements?

A

Chromatin barriers where methylation stops

23
Q

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

A

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

24
Q

What is imprinting?

A

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

25
Q

How does imprinting occur?

A

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

26
Q

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

A

Maternal

27
Q

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

A

Paternal

28
Q

How does the X chromosome become inactivated?

A

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

29
Q

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

A

False– a few areas are not

30
Q

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

A

True

31
Q

What is uniparental dismony?

A

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

32
Q

What is beckwith-Wiedemann syndrome?

A

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)

33
Q

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

A

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

34
Q

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

A

Angelman syndrome–unusual facial features, SZs, MR

35
Q

How does hypermethylation cause CA?

A

Silencing a tumor suppressor gene

36
Q

How does hypomethylation cause CA?

A
  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
37
Q

What is systemic lupus erythematosus?

A

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

38
Q

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

A
  1. Histone deacetylase inhibitors

2. DNA methyltransferase inhibitors (5-azacytidine)

39
Q

What is 5-azacytidine used for?

A

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

40
Q

What is Rett syndrome?

A

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

41
Q

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

A
  1. Histones become methylated
  2. Methylated histones bind to HP1 proteins
  3. HP1 proteins bind to histone methyltransferases, propagating the effect
42
Q

What is the cause for Lupus?

A

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

43
Q

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

A

promotes expression of silienced genes in chronic lymphocytic leukemia

44
Q

How can hypermethylation be reversed?

A

DNMT inhibitor aza-cytidine

45
Q

How can excessive chromatin silencing be reversed?

A

HDAC inhibitors

Enzymes (24 decks)

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