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Biochem Quiz 5 > Epigenetics > Flashcards

Epigenetics Flashcards

1
Q

Epigenetics

A

the inheritance of gene “states” (or potential for genes to be expressed) through mitosis predominantly

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2
Q

Biochemical mechanisms of epigenetic gene regulation (3)

A
  1. DNA methylation 2. histone covalent modification 3. Chromative remodeling complexes
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3
Q

genetics

A

inheritance of genes through alleles that determine a given phenotype (allele is inherited in a predictable way)

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4
Q

Why is epigenetics important for medicine?

A

Modifications are reversible so they can be targeted for drug therapy

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5
Q

How are epigenetic changes inherited?

A

through mechanisms that influence chromatin structure

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6
Q

euchromatin

A

regions of chromatin that are less condensed

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7
Q

heterochromatin

A

regions of chromatin that are highly condensed

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8
Q

constitutive heterochromatin

A

regions of chromatin that are always highly condensed

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9
Q

facultative heterochromatin

A

euchromatic regions that can assume a more condensed chromatin organization

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10
Q

Mechanism of DNA methylation

A

DNA methyltransferases covalently attach a methyl group to the # 5 carbon of cytosine in CpG dinucleotides

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11
Q

How is DNA methylation heritable?

A

DNA methyltransferase 1(DNMT1) copies methylation marks with the DNA replication complex onto the new daughter strand based on methylation of the parent strand (place for mistakes to happen/differences in gene expression)

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12
Q

How can DNA methylation be reversed?

A

group of enzymes (TET1, TET2, TET3) convert methyl group to -OH and then make to normal (H)

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13
Q

Mechanisms for reversing CpG methylation patterns in the genome (2)

A
  1. passive loss via global/regional inhibition of DNMT1 during replication (slow) 2. Active demethylation by TET enzymes (fast)
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14
Q

CpG island

A

region of DNA that have CpG associated with regulatory genes (important site for inheritance)

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15
Q

What is the general effect of DNA methylation on DNA?

A

generally correlates with condensed chromatin and transcriptional repression

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16
Q

How does DNA methylation directly affect gene transcription?

A

methyl groups on cytosines prevent DNA-binding proteins from interacting with their binding sites on chromatin

17
Q

How does DNA methylation indirectly affect gene transcription?

A

methyl-cytosine binding proteins can recruit protein complexes that act to repress transcription and reduce expression of the gene

18
Q

How can histones be modified? (4 major ones)

A
  1. Acetylation 2. methylation 3. phosphorylation 4. ubiquination ON TAILS OF HISTONES
19
Q

Mecahnism of the direct effect of Histone Acetyl Transferases (HATs)

A

HAT adds acetyl group to lysine which changes its +1 charge to a neutral charge which changes DNA structure (less condensed)

20
Q

General effects of histone acetylation on chromatin organization and gene transcription

A
  1. acetylation correlates with less condensed chromatin and active gene transcription 2. histone deacetylation correlates with condensed chromatin and transcriptional repression
21
Q

What is the indirect effect of HATs?

A

acetyl-lysine is recognized by proteins called histone code readers and recruit proteins that influence transcription

22
Q

What is the mechanism of histone methylation?

A

Histone methyltransferases (HMTs) covalently attach a methyl group to lysine or arginine side chains (can add 1, 2, or 3 methyl groups).

23
Q

What is the difference between the lasting effects of acetylation and methylation?

A

methylation is more stable

24
Q

How is histone methylation reversed?

A

Histone demethylases can reverse the effect of HMTs

25
Q

How does histone methylation affect chromatin organization and gene transcription?

A

methyl-lysine side chains are recognized by proteins that recuit protein complexes that will influence gene expression

26
Q

How do chromatin remodeling complexes affect gene expression?

A

they break non-covalent histone-DNA bonds which allows them to move the nucleosome on the chromosome - this can be activating or repressing

27
Q

How are histone modifications heritable?

A

histone strands can be modified. They will be randomly redistributed among parent and daughter strands during replication. The enzyme will recognize the modified histones and modify the histones around it, which often creates identical epigentic marks on each daughter strand. IMPORTANT that enzyme that makes the mark, also recognizes the mark.

28
Q

X chromosome Inactivation

A

within any given female cell, one of the X chromosomes will shut down one or the other X chromosome in the cell (mosaic pattern of expression)

29
Q

Mechanism of X chromosome inactivation

A

long non-coding RNA coats one X chromosome and starts mecahnism to shut it down (eventually becomes irreversible) - DNA methylation is important in the later stages and in propagation of the inactive X during mitosis

30
Q

Genomic Imprinting

A

DNA methylation during embryonic development of germ cells that is “remembered” from parent DNA (affects about 70 genes).

31
Q

Process of Genomic Imprinting in the Embryo

A

Important that after fertilization, the egg is stripped of all DNA methylation marks except for imprinted genes. Once the embryo has a gender, the DNA will be marked as maternal or paternal and turned on or off through imprinting.

32
Q

Example of effects of mutations on imprinted genes in two sydromes

A

Prader-Willi/Angelman Syndrome - same region, but AS has an affected maternal strand and PWS has an irreversibly repressed paternal strand - methylation is at the core of how this occurs

33
Q

Why is epigentics important in Tissue Development?

A

same mechanisms are used to create differentiation amongst tissue types to maintain cell identity (also revesible - can create stem cells!)

34
Q

How do cancer cells use epigenetics?

A

Can use methylation to inactivate tumor supressor genes (p16) so that the cell can grow uncontrollably

35
Q

Two examples of epigentic drugs used in clinics right now

A

Decitabine (inhibits DNMT1) and HDAC inhibitors

Biochem Quiz 5 (2 decks)

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