Epigenetics Exam I

Question 1

Epigenetics was first defined by whom?

Answer 1

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

Question 2

Gene Regulation describes what?

Answer 2

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

Question 3

Current definition of Epigenetics

Answer 3

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

Question 4

Heredity

Answer 4

transmission of traits from parents to offspring

Question 5

Heritability

Answer 5

genetic variance / phenotype variance

Question 6

How does epigenetics work?

Answer 6

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

Question 7

Major theoretical challenge

Answer 7

inheritance of acquired characters

Question 8

Gene Regulatory Network

Answer 8

hard wired

genetic relationships between DNA sequences and their products

Question 9

Attractors

Answer 9

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

Question 10

Chromatin Structure

Answer 10

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

Question 11

Chromatin

Answer 11

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

Question 12

Chromosomes

Answer 12

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

Question 13

Nucleosome

Answer 13

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

Question 14

Histones

Answer 14

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

Question 15

Major types of Chromatin Structure

Answer 15

Heterochromatin

Euchromatin

Question 16

Heterochromatin

Answer 16

highly condensed, usually inactive transcriptionally

Question 17

Types of heterochromatin

Answer 17

constituitive and falcutative

Question 18

Constitutive

Answer 18

condensed in all cells

Question 19

Facultative

Answer 19

Condensed in only some cells and relaxed in other cells

Question 20

Euchromatin

Answer 20

relaxed, usually active transcriptionally

Question 21

How can chromatin structure affect transcription?

Answer 21

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

Question 22

Mechanisms that can regulate chromatin patterns

Answer 22

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

Question 23

Chromatin Remodeling

Answer 23

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

Question 24

Epigenetic modification of DNA and histones regulate?

Answer 24

nucleosome occupancy and repositioning- histone modification and DNA methylation

Question 25

Histones

Answer 25

proteins that package DNA

Question 26

Comprise the Histone Octamer

Answer 26

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

Question 27

Runs between nucleosomes

Answer 27

Linker DNA | held by H1

Question 28

Negative charge of DNA is held by what?

Answer 28

positive charge of Amide group in histone AA

Question 29

What are core octamer and associate DNA

Answer 29

histone chaperones and other proteins that assemble the histone

Question 30

Types of histone modification

Answer 30

Non covalent modification | Covalent modification

Question 31

Non covalent modification

Answer 31

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

Question 32

Covalent Modification

Answer 32

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

Question 33

Major types of modification that effect trasncription

Answer 33

Acetylation Methylation Phosphorylation

Question 34

Small role in transcription

Answer 34

Ubiquination Sumoylation Ribosylation

Question 35

Chromatin remodeling

Answer 35

proteins that act to change structure

Question 36

Chromatin Modification

Answer 36

spontaneous nucleosome conformation changes- not understood

Question 36

SRCAP

Answer 36

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

Question 37

H2A.Z

Answer 37

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

Question 38

Histone variants

Answer 38

Genetically different May cause epigenetic differences Different AA sequences

Question 39

Histone PTM

Answer 39

Acetylation | Methylation

Question 40

Can occur at the same time

Answer 40

Histone variants and PTAs

Question 41

Cancer has what kind of causes and effects?

Answer 41

Epigenetic and Genetic | Epi- DNA methylation and history modification , histone variants

Question 42

Known to associate with cancer

Answer 42

Histone and histone PTM

Question 43

DNA replication dependent histones

Answer 43

``` 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 ```

Question 44

DNA replication independent

Answer 44

``` 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 ```

Question 45

Types of PTM

Answer 45

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

Question 46

H2A.Z

Answer 46

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

Question 47

H2A.Z-1 and 2

Answer 47

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

Question 48

Homotypic

Answer 48

Nucleosomes octamer with 2 identical h2a

Question 49

Heterotypic

Answer 49

Nucleosomes octamer with 2 different h2a

Question 50

Histone H2A.Z PTM

Answer 50

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