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Epigenetics Flashcards

1
Q

What is epigenetic phenomena?

A

Heritable self-perpetuating changes in gene expression not caused by base pair sequence changes

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2
Q

What is usually involved in epigenetic phenomena?

A

Modified cytosine residues, modified histone tails in chromatin, small RNAs

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3
Q

What are the three major epigenetic mechanisms?

A

Reverse modifications of DNA by addition or removal of methyl groups
Chromatin remodeling or removal of histone proteins
Regulation of gene expression by noncoding RNA molecules

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4
Q

What is genomic imprinting?

A

Phenomenon in which expression of an allele depends on the parent that transmits is

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5
Q

What does imprinting mean?

A

Silenced

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6
Q

What does it mean if an allele is paternally imprinted?

A

Paternal allele not transcribed

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7
Q

What does is a maternally imprinted allelee?

A

Maternal allele not transcribed

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8
Q

What is methylome?

A

Set of methylated nucleotides present in organism’s genome

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9
Q

When does methylation of DNA take place in mammals?

A

After replication and during differentiation

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10
Q

What is involved in methylation in mammals?

A

Addition of methyl group -CH3

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11
Q

What catalyzes methylation in mammals?

A

DNA methyltransferases (DNMTS)

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12
Q

Outline the process of DNA methylation

A

Methyltransferase enzymes catalzye the transfer of a methyl group from a methyl donor to cytosine, producing 5-methylcytosine

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13
Q

On which cytosine bases does methylation occur?

A

Those adjacent to guanine base

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14
Q

What is the guanine-adjacent cytosine combination called?

A

CpG dinucleotides, clustered in CpG islands

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15
Q

How are CpG islands adjacent to essential and cell-specific genes characterized?

A

Unmethylated

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16
Q

Where are most methylate CpG dinucleotides located?

A

In repetitive DNA sequences of heterochromatic regions

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17
Q

How do CpG islands contribute to transcription?

A

CpG islands are usually unmethylated and located near a promoter. An activator binds unmethylated CpG islands, the chromain is open and transcription is activated.

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18
Q

How can gene expression be silenced at CpG islands?

A

CpG islands become methylated.
Repressors called methyl-CpG-binding proteins MeCPs bind to methylated CpG islands and close the chromatin structure

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19
Q

What are the two processes that activate or repress transcription?

A

Chromatin remodeling and histone modification

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20
Q

What is chromatin remodeling?

A

ATP powered protein complexes move, remove or alter nucleosomes

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21
Q

What is histone modification?

A

Covalent posstranslational modifications of amino acids near histone proteins

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22
Q

How can the addition of acetyl, methyl and phosphate groups alter chromatin structure?

A

Makes genes on nucleosomes with modified histones accessible or inaccessible for transcription

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23
Q

What does histone acetylation do?

A

Opens up chromatin structure, making genes available for transcription

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24
Q

What is the histone code?

A

Sum of complex patterns and interactions of histone modifications

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25
What produces noncoding RNAs?
Genome transcription
26
What are noncoding RNAs?
RNAs that are transcribed but not translated
27
Describe the two groups of ncRNAs
Short ncRNAs <31 nucleotides Long ncRNAs > 200 nts
28
What is monoallelic expression?
Only one allele is transcribed, the other is transcriptionally silent
29
Differentiate between the three major classes of monoallelic expression.
One class involves genes expressed in parent-of-origin pattern Two classes involve random monoallelic expression
30
What are epimutations?
Mutations in imprinted genes cause by dysfunctional epigenetic changes
31
What can epimutations cause?
Heritable changes in gene activity
32
How is cytosine methylation pattern copied during DNA replication?
Special DNMT at the replication fork methylates the newly synthesized DNA strand
33
What are examples of human disorders caused by imprinting defects?
Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome
34
What do most imprinted-related genes encode?
Growth factors or other growth-regulating genes
35
What is Beckwith-Wiedemann syndrome (BWS)
Prenatal overgrowth disorder
36
What are characteristics of BWS?
Enlarge organs, high birth weight, predisposition to cancer
37
Where are the genes of BWS imprinted?
Epigenetically imprinted on short arm of chromosome 11
38
Describe the genes of BWS
Have abnormal methylation patterns which result in altered patterns of gene expression
39
What happens to epigenetic imprints during meiosis?
Erased and new ones are set based on the sex of the organism
40
What are the two mechanisms through which imprinting occurs?
Insulator and ncRNA
41
Describe the insulator mechanism of imprinting
ICR is an insulator that controls transcription of lgf2 gene Nonmethylated maternal insulator is functional; binds CTCF and transcription is silenced Methylated paternal insulator is nonfunctional and transcription is active
42
Explain the ncRNA mechanism of imprinting
ICR contains a noncoding RNA whose transcription is controlled by CpG islands Nonmethylated paternal CpG island allows production of Air ncRNA; transcription is silenced Methylated maternal CpG island prevents production of Air; transcription is active
43
How is DNA methylation associated with cancer?
Cancer cells have much lower levels of methylation than normal cells from the same tissue Complex changes in DNA methylation patterns associated with cancer
44
What is a property of all cancers examined to date?
Genomic hypomethylation
45
What does DNA hypomethylation do?
Reverses silencing of genes Leads to unrestricted transcription Relaxes control over imprinted genes
46
What are some human cancer-related genes inactivated by hypermethylation
BRCA1 APC MLH1 RB1 AR ESR1
47
Hypermethylation of which gene is associated with breast and ovarian cancers?
BRCA1
48
Hypermethylation of which gene is associated with colorectal and duodenal cancers?
APC
49
Hypermethylation of which gene is associated with colon and stomach cancers?
MLH1
50
Hypermethylation of which gene is associated with retinoblastoma and osteosarcoma cancers?
RB1
51
Hypermethylation of which gene is associated with prostate cancers?
AR
52
Hypermethylation of which gene is associated with breast and colorectal cancers?
ESR1
53
What factors interact and are involved with the development and maintenance of malignant cancer growth?
Gene mutations Hypomethylation Hypermethylation Overexpression of oncogenes Silencing of tumor-suppressor genes
54
What three lines of evidence support the role of epigenetic alterations in cancer?
1. Global hypomethylation may cause genome instabilitiy and large scale changes characteristic of cancer 2. Epigenetic mechanism can replace mutations to silence tumor suppressor genes or activate oncogenes 3. Epigenetic modifications can silence multiple genes, making them more effective in transforming normal cells into malignant cells
55
Give an example of an epigenetic drig approved by the FDA
Vidaza
56
What does Vidaza treat?
Myelodysplastic syndrome
57
What is myelodysplastic syndrome a precurose to?
Leukemia and acute myeloid leukemia
58
What is Vidaza?
Analog of cytidine
59
How does Vidaza work?
Methyltranserases bind to analog preventing DNA methylation in cancer cells
60
What are characteristics of agouti mice?
Yellow, obese
61
What caused the agouti gene?
Allele occurred when a retrotransposon containing a promoter region and CpG island jumped upstream of agouti
62
How does methylation contribute to the phenotype of the agouti allele?
When CpG islands is unmethylated, high levels of agouti mRNA are transcribed from retrotransposon promoter - yellow When CpG island is methylated, transcription occurs from the normal agouti promoter - gray
63
What is correlated with coat colour in mice?
Degree of CpG methylation of the TE insertion
64
How does maternal diet affect coat colour in mice?
Agouti mice whose mothers were fed a diet rich in methyl groups were darker on average
65
What is transgenerational epigenetic inheritance?
Environmentally induced trait appearing in descendants of an individual whose germ line was not directly exposed to the stimulus
66
What is intergenerational epigenetic inheritance?
Environmentally induced trait that is displayed only in the child, or child and grandchild, of an originally expose female, or the child of an exposed male

BIO207 (9 decks)

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