Exam #5: Epigenetic Phenomena Flashcards Preview

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Flashcards in Exam #5: Epigenetic Phenomena Deck (29):
1

Define Epigenetics

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

2

De-novo Methylation

- "Writing"
- De-novo DNA methyltransferase
- Methylate cytosine in response to cell signaling

3

Maintenance Methylation

- "Copying"
- Maintenance Methyltransferase
- Copy the methylation pattern from an old DNA strand to a new DNA strand

4

CpG Islands

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

5

Hypomethylation & Genome Stability

- Expression of genes normally silenced by methylation
- Causes the reactivation of transposable elements, leading to somatic recombination & genomic instability

6

HP1

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

7

Boundary Elements

- Chromatin barriers
- Separate active and inactive genomic regions

8

Imprinting

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

9

Prader-Willi Syndrome

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

10

Angelmann Syndrome

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

11

Parent Of Origin Effect

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

12

Uniparental Disomy

- 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

13

Epigenetics & Cancer

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

14

5-Azacytidine

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

15

How is epigenetic information stored?

On chromatin in the form of:

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

16

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

- 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

17

"Writer Enzyme"

De-novo DNA methyltransferase (DNMT3 a&b)

18

"Copier Enzyme"

Maintenance methyltransferase (DNMT1)

19

CpG Dinucleotide Repats

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

20

Hypermethylation

Shuts down the expression of genes close to CpG islands

21

Transposable Element

DNA sequence that can change its position within the genome

22

"Readers"

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

23

Rett Syndrome

- 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

24

What are the four ways that histones can be modified?

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

25

HAT

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

26

HDAC

- Histone deacetylase
- Increases histone binding affinity
- Silences transcription

27

X-Chromosome Inactivation

- 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

28

Beckwith-Weidemann Syndrome

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

29

SLE

- 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