Exam #5: Epigenetic Phenomena

Question 1

Define Epigenetics

Answer 1

Study of stable, heritable changes in gene expression without changing DNA sequence

Question 2

De-novo Methylation

Answer 2

• “Writing”
• De-novo DNA methyltransferase
• Methylate cytosine in response to cell signaling

Question 3

Maintenance Methylation

Answer 3

• “Copying”
• Maintenance Methyltransferase
• Copy the methylation pattern from an old DNA strand to a new DNA strand

Question 4

CpG Islands

Answer 4

• Clusters of unmethylated CpG dinucleotides found close to the 5’ region of genes
• Methylation shuts down expression of neighboring genes

Question 5

Hypomethylation & Genome Stability

Answer 5

• Expression of genes normally silenced by methylation

- Causes the reactivation of transposable elements, leading to somatic recombination & genomic instability

Question 6

HP1

Answer 6

• Deacetylated histones are methylated
• Methylated histones bind HP1
• HP1 binds histone methylase, which allows chromatin inactivation to spread

Question 7

Boundary Elements

Answer 7

• Chromatin barriers

- Separate active and inactive genomic regions

Question 8

Imprinting

Answer 8

• DNA silencing that marks a chromosome as having come from the mother or father
• Occurs during gametogenesis

Question 9

Prader-Willi Syndrome

Answer 9

• Imprinting problem
• Deletion on paternal chromosome 15
• Symptoms: Obesity, excessive food seeking, hypogonadism, & mental retardation

Question 10

Angelmann Syndrome

Answer 10

• Imprinting problem
• Deletion on maternal chromosome 15
• Symptoms: Fascial dysmorphia, seizures, movement & gait disorder, and severe mental retardation

Question 11

Parent Of Origin Effect

Answer 11

• Repression of genes is dependent on chromosomes parent of origin
• Female makes chromosomes look maternal
• Male makes chromosomes look paternal

Question 12

Uniparental Disomy

Answer 12

• When a person receives two copies of a chromosome from one parent, and no copies from the other parent
• Can happen with trisomy & loss of surplus chromosome, if kept chromosomes are from the same parent
• Leads to problems with imprinting

Question 13

Epigenetics & Cancer

Answer 13

• Global hypermethylation can cause cancer via silencing of tumor suppressor genes
• Hypomethylation can lead to genomic instability that initiates and propagates cancer

Question 14

5-Azacytidine

Answer 14

• DNMT1 inhibitor
• Causes hypomethylation
• Counteracts malignancies associated with hypermethylation including Acute Myeloid Leukemia

Question 15

How is epigenetic information stored?

Answer 15

On chromatin in the form of:

1) Methylation pattern of cytosine bases
2) Covalent modification of histones

Question 16

What does the cell need to ensure the writing, retention, & correct interpretation of epigenetic information?

Answer 16

• Writers, enzymes that methylate cytosine in response to signals
• Copiers, enzymes that copy the methylation pattern from old DNA to newly synthesized DNA
• Readers, enzymes that recognize methylated stretches of DNA

Question 17

“Writer Enzyme”

Answer 17

De-novo DNA methyltransferase (DNMT3 a&b)

Question 18

“Copier Enzyme”

Answer 18

Maintenance methyltransferase (DNMT1)

Question 19

CpG Dinucleotide Repats

Answer 19

• Commonly found in highly repetitive DNA, telomeres, centromeres
• Silenced by DNA methylation on cytosine

Question 20

Hypermethylation

Answer 20

Shuts down the expression of genes close to CpG islands

Question 21

Transposable Element

Answer 21

DNA sequence that can change its position within the genome

Question 22

“Readers”

Answer 22

• Methylcytosine Binding Proteins
• Interact with repressors of transcription
• HDACs

Question 23

Rett Syndrome

Answer 23

• X-linked dominant disorder
• Caused by defect in methylcytosine binding protein (MECP2)
• Normal development until ~6 months, then hypotonic, loss of hand control, autism-like with hand wringing, teeth grinding, & hyperventilation

Question 24

What are the four ways that histones can be modified?

Answer 24

1) Acetylation
2) Methylation
3) Phosphorylation
4) Ubiquitination

Question 25

HAT

Answer 25

• Histone acetyltransferase
• Acetylate histones
• Decrease binding to DNA
• Increase transcription

Question 26

HDAC

Answer 26

• Histone deacetylase
• Increases histone binding affinity
• Silences transcription

Question 27

X-Chromosome Inactivation

Answer 27

• In the X-chromosome inactivating center (XIC) there is a gene designated the inactive X-specific transcript (XIST)
• XIST RNA associates with chromosome and mediates inactivation of most of the chromosome
• Methylation causes inactivation

Question 28

Beckwith-Weidemann Syndrome

Answer 28

• Uniparental disomy of chromosome 11
• Causes an overabundance of insulin-like growth factor 2
• Symptoms: kidney, adrenal, & liver problems resulting in hypoglycemia

Question 29

SLE

Answer 29

• Systemic Lupus Erythematosus
• Abnormal T-cell function believed to be the root cause
• Genome of T-cells is hypomethylated & DNMT1 is reduced
• Leads to re-expression of silenced genes