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BIO207 > Epigenetics > Flashcards

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
Q

What produces noncoding RNAs?

A

Genome transcription

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26
Q

What are noncoding RNAs?

A

RNAs that are transcribed but not translated

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27
Q

Describe the two groups of ncRNAs

A

Short ncRNAs <31 nucleotides
Long ncRNAs > 200 nts

28
Q

What is monoallelic expression?

A

Only one allele is transcribed, the other is transcriptionally silent

29
Q

Differentiate between the three major classes of monoallelic expression.

A

One class involves genes expressed in parent-of-origin pattern
Two classes involve random monoallelic expression

30
Q

What are epimutations?

A

Mutations in imprinted genes cause by dysfunctional epigenetic changes

31
Q

What can epimutations cause?

A

Heritable changes in gene activity

32
Q

How is cytosine methylation pattern copied during DNA replication?

A

Special DNMT at the replication fork methylates the newly synthesized DNA strand

33
Q

What are examples of human disorders caused by imprinting defects?

A

Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome

34
Q

What do most imprinted-related genes encode?

A

Growth factors or other growth-regulating genes

35
Q

What is Beckwith-Wiedemann syndrome (BWS)

A

Prenatal overgrowth disorder

36
Q

What are characteristics of BWS?

A

Enlarge organs, high birth weight, predisposition to cancer

37
Q

Where are the genes of BWS imprinted?

A

Epigenetically imprinted on short arm of chromosome 11

38
Q

Describe the genes of BWS

A

Have abnormal methylation patterns which result in altered patterns of gene expression

39
Q

What happens to epigenetic imprints during meiosis?

A

Erased and new ones are set based on the sex of the organism

40
Q

What are the two mechanisms through which imprinting occurs?

A

Insulator and ncRNA

41
Q

Describe the insulator mechanism of imprinting

A

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
Q

Explain the ncRNA mechanism of imprinting

A

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
Q

How is DNA methylation associated with cancer?

A

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
Q

What is a property of all cancers examined to date?

A

Genomic hypomethylation

45
Q

What does DNA hypomethylation do?

A

Reverses silencing of genes
Leads to unrestricted transcription
Relaxes control over imprinted genes

46
Q

What are some human cancer-related genes inactivated by hypermethylation

A

BRCA1
APC
MLH1
RB1
AR
ESR1

47
Q

Hypermethylation of which gene is associated with breast and ovarian cancers?

A

BRCA1

48
Q

Hypermethylation of which gene is associated with colorectal and duodenal cancers?

A

APC

49
Q

Hypermethylation of which gene is associated with colon and stomach cancers?

A

MLH1

50
Q

Hypermethylation of which gene is associated with retinoblastoma and osteosarcoma cancers?

A

RB1

51
Q

Hypermethylation of which gene is associated with prostate cancers?

A

AR

52
Q

Hypermethylation of which gene is associated with breast and colorectal cancers?

A

ESR1

53
Q

What factors interact and are involved with the development and maintenance of malignant cancer growth?

A

Gene mutations
Hypomethylation
Hypermethylation
Overexpression of oncogenes
Silencing of tumor-suppressor genes

54
Q

What three lines of evidence support the role of epigenetic alterations in cancer?

A
  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
Q

Give an example of an epigenetic drig approved by the FDA

A

Vidaza

56
Q

What does Vidaza treat?

A

Myelodysplastic syndrome

57
Q

What is myelodysplastic syndrome a precurose to?

A

Leukemia and acute myeloid leukemia

58
Q

What is Vidaza?

A

Analog of cytidine

59
Q

How does Vidaza work?

A

Methyltranserases bind to analog preventing DNA methylation in cancer cells

60
Q

What are characteristics of agouti mice?

A

Yellow, obese

61
Q

What caused the agouti gene?

A

Allele occurred when a retrotransposon containing a promoter region and CpG island jumped upstream of agouti

62
Q

How does methylation contribute to the phenotype of the agouti allele?

A

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
Q

What is correlated with coat colour in mice?

A

Degree of CpG methylation of the TE insertion

64
Q

How does maternal diet affect coat colour in mice?

A

Agouti mice whose mothers were fed a diet rich in methyl groups were darker on average

65
Q

What is transgenerational epigenetic inheritance?

A

Environmentally induced trait appearing in descendants of an individual whose germ line was not directly exposed to the stimulus

66
Q

What is intergenerational epigenetic inheritance?

A

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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