Epigenetics Exam I Flashcards

1
Q

Epigenetics was first defined by whom?

A

Conrad Waddington in 1942 as a branch of biology which studies the casual interactions between genes and their products which bring the phenotype into being

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2
Q

Gene Regulation describes what?

A

How genes are controlled
How do they know what tissue they are in
How do they know what type of cell they are
How do you maintain cell identity and function

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3
Q

Current definition of Epigenetics

A

Study of changes in gene function that are mitotically and or meiotically heritable and that do not entail a change in the DNA sequence
The change in gene function without change in DNA sequence
Changes in phwnotype not caused by changes in DNA

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4
Q

Heredity

A

transmission of traits from parents to offspring

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5
Q

Heritability

A

genetic variance / phenotype variance

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6
Q

How does epigenetics work?

A

control gene expression acheived through semi reversible covalent modification of DNA bases and the proteins that package DNA and the proteins in the surrounding area of the of the nucleus

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7
Q

Major theoretical challenge

A

inheritance of acquired characters

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8
Q

Gene Regulatory Network

A

hard wired

genetic relationships between DNA sequences and their products

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9
Q

Attractors

A

in dynamic system, a set of physical properties toward which a system tends to evolve regardless of starting conditions of the system.

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10
Q

Chromatin Structure

A

DNA interaction with histones and non histone proteins produces suffiecient level of compaction to fit into a cell nucleus

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11
Q

Chromatin

A

generic term for any complex of DNA and protein found in a nucleus of a cell

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12
Q

Chromosomes

A

separate pieces of chromatin that behave as a unit during cell division. Versatile, modular strucutre for packaging DNA that supports flexibilty of form and funciton

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13
Q

Nucleosome

A
Basic unit of chromatin 
DNA, histones, non histone protein
Package , hold DNA
Where a particular locus is in 3D inside the nucleus
Formed from a histone octamer and DNA
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14
Q

Histones

A

Proteins
H1,H2,H2B,H3,H4
Like stacked blocks
H1 holds end of DNA after it has wrapped around octamer

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15
Q

Major types of Chromatin Structure

A

Heterochromatin

Euchromatin

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16
Q

Heterochromatin

A

highly condensed, usually inactive transcriptionally

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17
Q

Types of heterochromatin

A

constituitive and falcutative

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18
Q

Constitutive

A

condensed in all cells

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19
Q

Facultative

A

Condensed in only some cells and relaxed in other cells

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20
Q

Euchromatin

A

relaxed, usually active transcriptionally

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21
Q

How can chromatin structure affect transcription?

A

Hetero- reduces transcription
Nucleoomes can sequester promotersm make them inaccessible to RNA polymerase and transcription factors
Changes can be inherited from gen to another
Faithfully transmitted through mitosis

22
Q

Mechanisms that can regulate chromatin patterns

A

Histone modifications

  1. N terminal tails of histones H3 and 4 can be modified
  2. Methylation, acetylation, phosphorylation, ubiquination
  3. Affect nucleosome interaction with other nucleosomes and with regulatory proteins
  4. Affect higher order chromatin structure

Histone variants can cause diferent nucleosome structures

Remodeling complexes can alter nucleosome patterns: change accessibility of promoter sequences and remove or reposition promoter blocking nucleosomes

23
Q

Chromatin Remodeling

A

ATP dependent nucleosome remodeling factor that modulates acces of transcription factors to DNA

Chromatin Remodeling Structures- recruited to particular regions by site specific DNA biding proteins, reposition of nucleosomes

Chromosome Modificatio n
spontaneous nucleosome conformation changes

24
Q

Epigenetic modification of DNA and histones regulate?

A

nucleosome occupancy and repositioning- histone modification and DNA methylation

25
Q

Histones

A

proteins that package DNA

26
Q

Comprise the Histone Octamer

A

H2A, H2B,H3,H4
that wrap 147 bp of DNA
Fundamental unit of nucleosome

27
Q

Runs between nucleosomes

A

Linker DNA

held by H1

28
Q

Negative charge of DNA is held by what?

A

positive charge of Amide group in histone AA

29
Q

What are core octamer and associate DNA

A

histone chaperones and other proteins that assemble the histone

30
Q

Types of histone modification

A

Non covalent modification

Covalent modification

31
Q

Non covalent modification

A

effects how DNA interacts with the histone proteins leading to the relocation of the histones on DNA

32
Q

Covalent Modification

A

effects positioning of histones but does so through modification of the N terminal tails particularly the H3 and 4 tails

33
Q

Major types of modification that effect trasncription

A

Acetylation
Methylation
Phosphorylation

34
Q

Small role in transcription

A

Ubiquination
Sumoylation
Ribosylation

35
Q

Chromatin remodeling

A

proteins that act to change structure

36
Q

Chromatin Modification

A

spontaneous nucleosome conformation changes- not understood

36
Q

SRCAP

A

Enzyme regulated in concert with androgen receptor
Catalyzes H2A.Z and H2B
Deregulation can lead to cancer

37
Q

H2A.Z

A

Histone variant
Different version of h2a
Different DNA sequence
H2A.Z 1 and 2 , variable versions of H2A.Z

38
Q

Histone variants

A

Genetically different
May cause epigenetic differences
Different AA sequences

39
Q

Histone PTM

A

Acetylation

Methylation

40
Q

Can occur at the same time

A

Histone variants and PTAs

41
Q

Cancer has what kind of causes and effects?

A

Epigenetic and Genetic

Epi- DNA methylation and history modification , histone variants

42
Q

Known to associate with cancer

A

Histone and histone PTM

43
Q

DNA replication dependent histones

A
H1,2 a and b, 3, 4
Exist in gene clusters
Massively expressed during s phase 
No poly a tail or introns 
Several variants exists
44
Q

DNA replication independent

A
H1,2 a and b, 3, 4
Lower expression 
Has poly a tail and introns 
Expressed throughout cell cycle 
Replacement histone variants that replace one or more of the independent ones in certain nucleosomes
45
Q

Types of PTM

A

Long range - PTM that occurs commonly throughout the cell/genome
Specific - occur at particular loci / gene

46
Q

H2A.Z

A

Ancient replacement variant - present in yeast
Encoded by a single gene throughout vertebrates
Needed for survival in model organisms
Acts as depressor and activator
Helps recruits RNA poly II
Poising genes for expression
Not necessary for transcription
Tx activation requires evicting h2a.z containing nucleosomes near tss

47
Q

H2A.Z-1 and 2

A

Different promoters, 5’utr , intron/exon organization, differ by three amino acids

48
Q

Homotypic

A

Nucleosomes octamer with 2 identical h2a

49
Q

Heterotypic

A

Nucleosomes octamer with 2 different h2a

50
Q

Histone H2A.Z PTM

A

H2a.z being activator or repress or depends on PTM
of h2a.z or other histones in nucleosomes including h2a.z

H2a.z acetylation found in promoters of actively transcribed genes
Non acetylation in poised promoters of genes not being transcribed

Relationship between PTM and gene expression