Chromosome and Epigenetics

Question 1

What is epigenetics?

Answer 1

Describes the stable inheritance of phenotypes, that relies on specific gene expression profiles but with no change to the DNA sequence

Question 2

What is chromatin?

Answer 2

Chromatin = protein + DNA
Proteins are known as histones: H3, H4, H2A, H2B and H1

Question 3

What are nucleosomes?

Answer 3

Consists of 146bp wrapped around a histone octamer (1 tetramer of H3 and H4 and two dimers of H2A and H2B). Surrounding the nucleosome core is a linker histone, H1, which can compact the nucleosomes into higher-order structures that further condense the DNA

Question 4

What is the difference between hetero- and euchromatin? (2)

Answer 4

• Heterochromatin is more tightly packed forms of DNA while euchromatin is the decondensed open form
• Hetero is transcriptionally inactive as opposed to the eu-

Question 5

What are the types of histone modifications? (2)

Answer 5

Histones have N and C terminal tails which can be modified post-transitionally
- Histone Acetylation
- Histone Modification

Question 6

Explain Histone acetylation

Answer 6

It is the addition of acetyl groups to specific amino acids (such as lysine) on specific histones

Triggers transcription. Acetylation removes the positive charge of histone tails which allows for looser structure

Question 7

Explain histone methylation

Answer 7

It is the addition of methyl groups to histone tails. Can be mono-,di- and trimethylated.

Specific lysine or arginine residues are commonly modified on H3 and H4. Can indicate active or inactive chromatin.

Question 8

Give examples of histone methylation and its effect (2)

Answer 8

• H3K4 tri-methylation is associated with active genes
• H3K9 tri-methylation is a mark of heterochromatin added by Suvar3-9 and recognised by heterochromatin protein 1

Question 9

What types of chromatin changes are associated with changes in gene activity? (3)

Answer 9

• Histone modification
• Histone remodelling
• Variant histones

Question 10

Give an example of a variant histone

Answer 10

CENP-A - variant of H3

Centromeric chromatin contains CENP-A which is where kinetochore form which will be the point of attachment.
Core Centromere surrounded by heterochromatin

Question 11

Explain the theory behind variegated eyes in drosophila

Answer 11

In the rearrangement and inversion of the white gene in drosophila, the white gene now finds itself near the heterochromatic centromere.

In some cells, the heterochromatin can “spread” to the neighbouring euchromatin and silence the white gene.

Question 12

What does variegated eyes show about epigenetic silencing?

Answer 12

This illustrates to two features of epigenetic silencing: expression of a gene can be repressed by virtue of its position in chromosome and that epigenetic silencing can be inherited.

Question 13

What is the effect of methylating DNA?

Answer 13

Methylation of CG dinucleotides is a repressive and heritable epigenetic mark

Question 14

What are CpG islands?

Answer 14

Unmethylated CG dinucleotides are found in clusters near gene promoters.

High CpG and thus GC content, unmethylated and open chromatin.

Question 15

How does dosage compensation occur in sex chromosomes?

Answer 15

X inactivation occurs through heterochromatin formation
CpG islands of X inactivated genes become methylated except at Xist.

Question 16

What is the basis of chromosomal segregation?

Answer 16

It is mediated by interactions between a DNA-bound protein structure called the kinetochore and spindle microtubule

Microtubules pull chromosomes via the kinetochores.

Question 17

What is cohesin?

Answer 17

It is a ring-shaped protein complex that holds sister chromatids together. Accumulates at the centromere

Cohesin is established during S phase. Cohesin ring will then be destroyed at meta/anaphase

Question 18

What is the difference between homologous chromosomes and sister chromatids?

Answer 18

• Homologous chromosomes are when one chromosome comes from mom and the other from dad
• Sister chromatids is a chromosome containing double-strand DNA (replicates of each other)

Question 19

How does segregation create huge diversity?

Answer 19

The way bivalents line up is random and can arrange either way with equal probability

Example.
if n = 23 (Human), 2^23 = 8 million possible eggs or sperms

Question 20

When does recombination happen?

Answer 20

In Prophase 1

Question 21

What is the synaptonemal complex?

Answer 21

Protein lattice involved in stabilising pairing of homologous chromosomes and promoting recombination

Question 22

What are the 5 subsections of Prophase 1?

Answer 22

1. Leptotene: Chromosomes begin to condense
2. Zygotene: Synapsis between homologous chromosomes begins. Formation of SC
3. Pachytene: Fully formed SC and stabilised. Crossover can now begin
4. Diplotene: SC disassembled and homologous chromosomes begin to migrate apart
5. Diakinesis: Termination of the condensing of chromosomes and nuclear membrane disintegrates

Question 23

Are all cohesins completely destroyed in metaphase 1?

Answer 23

No,
Cohesin is destroyed in meiosis I but protected at centromeres. This way sister chromatids are still connected

Question 24

What is aneuploidy?

Answer 24

Containing the wrong number of chromosomes.

Ex.
Monosomy –> chromosome loss (2n-1)

Question 25

What is nondisjunction?

Answer 25

The failure of segregation of homologous chromosomes or chromatids.

In which two chromosomes or chromatids incorrectly go to one pole and none to other

Question 26

Why is aneuploidy harmful?

Answer 26

In a euploid, the ratio of genes on a chromosome compared to the other chromosome is 1:1

Aneuploidy causes a 50% increase or decrease in gene dosage. In most genes there are no effects however in some genes it will be harmful

Question 27

What is the gene-dosage effect?

Answer 27

The more copies of the gene, the more transcripts are produced and thus the more of the corresponding protein product is made

Question 28

How do you determine which parent the aneuploidy comes from?

Answer 28

Use mini/microsatellites to determine where the genes come from. You can compare the mini/microsatellite to the parents to determine the origin of extra chromosomes

Look at the centromere because the DNA at the centromere rarely changes

Question 29

How do you determine when aneuploidy occurs?

Answer 29

If nondisjunction occurs in meiosis I,
all four products will be chromosomally abnormal. Two of the four products will have two copies of the chromosome and the other two will have no copies

If nondisjunction happens in meiosis II,
two of the four products will be unaffected by the event and two will be abnormal.

Question 30

How does the cohesin ‘fatigue’ hypothesis explain the maternal age effect?

Answer 30

In mitotic cycle, cohesin is established during S phase and degraded during meta/anaphase

IF cohesin rings are also established in S phase, not in other stages, in meiosis in human oocyte, the same molecules of cohesin have to stay on chromosome for decades.

This may explain maternal age effects –> once removed, cohesin can’t come back. As years go by, there are fewer cohesins.