Chromosomes

Question 1

What is each chromosome made of?

Answer 1

1 linear strand of DNA

Question 2

When is DNA most tightly packed?

Answer 2

When cells are dividing

Question 3

What is a karyotype?

Answer 3

No., size & shape of chromosomes in the nucleus

Question 4

What is different about the chromosomes in Klinefelter’s syndrome?

Answer 4

XXY

Question 5

What is a nucleosome?

How many times is the DNA wound per histone?

How many base pairs are wrapped around a histone?

Answer 5

Length of DNA coiled around a core of histones

1.67

147

Question 6

What are the 4 core histones?

What do 2 pairs of tetramers form when bound together?

Answer 6

H2A
H2B
H3
H4

An octamer

Question 7

What is a nucleosome made up of?

Answer 7

2 core histones
Linker DNA
H1 (a histone)

Question 8

How are nucleosomes dynamic?

Answer 8

1. Chromatin remodelling factors slide along DNA
2. Exchange histone octamers or subunits
3. Remove core histones
   - -> alters structure

Question 9

What is special about the histone tails that stick out?

Answer 9

They can be modified by chemical groups

e.g. 1-3 methyl groups, acetyl groups, phosphate groups

Question 10

Where are histone tails mostly methylated?

Answer 10

Lysines

• up to 3 methyl groups can be added to 1 lysine

Question 11

What happens to the chromatin when histone tails are methylated?

How does this affect gene expression?

Answer 11

Chromatin condenses

Genes repressed

Question 12

What happens to the chromatin when histone tails are acetylated?

How does this affect gene expression?

Answer 12

Chromatin de-condenses
- histones move further apart

Genes expressed

Question 13

How is heterochromatin self-propagating?

Answer 13

Chromatin modifications can spread along chromosomes

- methylated histones recruit more histone methylases

Question 14

What is the ‘position effect’?

Answer 14

A normally active gene is silenced because of proximity to heterochromatin after DNA breakage & re-joining
(translocation events)

Question 15

What are the other types of histone modifications?

Answer 15

> serine phosphorylation
Ubiquitination
SUMOlyation

Question 16

What are the 4 types of regulatory proteins that bind to marked proteins to read the ‘histone code’?

Answer 16

> chromatin remodelling complexes
transcription activators
transcription repressors
DNA damage repair complexes (H2A.X)

Question 17

What are epigenetics?

Who can they be passed between?

Answer 17

The study of heritable phenotype changes w/ no change in DNA sequence

> parent to offspring via germ cells
mother to daughter cells

Question 18

What can cause epigenetic imprints?

Answer 18

> Exposure to pollutants
Stress
Drugs
Famine?

Question 19

How can epigenetics lead to cancer?

Answer 19

Tumour suppressors hypermethylated
= silencer turned off
–> excessive cell division

Question 20

Describe DNA methylation in epigenetics

Answer 20

Adding methyl groups to DNA (CpG sites)

= represses gene transcription

Question 21

Give examples of when DNA methylation is essential for normal development

What is DNA methylation affected by?

Answer 21

> embryonic stem cells are largely de-methylated (pluripotent cells don’t require a lot of silencing)
methylation in cell differentiation

• diet
• environment
• ageing

Question 22

What are the functional links between histone & DNA methylation?

Answer 22

> Gene silencing
Histone lysine methylation DNA methylation
Histone 3??
Maintenance methylation

Question 23

What is maintenance methylation?

Answer 23

Maintaining methylation patterns on newly-synthesised DNA strands after replication

e.g. for a liver cell to remain as a liver cell it must inherit epigenetic marks

Question 24

Describe the higher-order chromatin packing

Answer 24

30nm fibre of nucleosomes are assembled into loops on protein scaffold
–> form coils of heterochromatin

Question 25

What are the 2 examples of territories within the nucleus that represent the spatial arrangement of chromatin?

Answer 25

LADs = Lamina-associated domains TADs = Topologically associated domains

Question 26

What are TADs formed by?

Answer 26

Cohesin | = ring-shaped protein complex that physically bundles chromatin

Question 27

What are TAD boundaries formed by?

Answer 27

CTCF (=CCTC-binding factor) = a transcription factor expressed in all cell types

Question 28

What are insulated neighbourhoods? What happens in these regions?

Answer 28

Chromosomal loop structures formed by the physical interaction of 2 DNA loci bound by CTCF and co-occupied by cohesin There is co-regulation of genes

Question 29

What are the 2 types of heterochromatin?

Answer 29

Facultative | Constitutive

Question 30

Describe facultative heterochromatin

Answer 30

= Parts of genome are silenced but have the potential to be expressed >may switch between hetero- & euchromatin states >modification of histones or DNA

Question 31

Describe constitutive heterochromatin

Answer 31

= remains condensed throughout cell cycle > highly repetitive sequences > may play role in chromatin structures > telomeres & centromeres

Question 32

What are telomeres?

Answer 32

Long repetitive sequences that protect the ends of chromosomes - TTAGGG x 2,500 in humans 11 kb at birth --> 4 kb in old age

Question 33

Why do telomeres get shorter?

Answer 33

DNA replication enzymes cannot replicate v ends of DNA strands - lose some telomeres w/ every cell division

Question 34

What is the 'hayflick limit'?

Answer 34

no. of times a human cell population will divide before cell division stops

Question 35

When don't telomeres get shorter? Why?

Answer 35

If the cells express telomerase e.g. germ cells, embryonic stem cells & cancer cells They add telomere repeat sequences to the end of telomeres

Question 36

What is a centromere?

Answer 36

A specialised DNA sequence of a chromosome that links a pair of sister chromatids = junction of replicated chromosomes

Question 37

What is the centromere the site of?

Answer 37

Where microtubules attach during mitosis | - at the kinetochore

Question 38

What can centromere instability result in?

Answer 38

Mis-segregation of chromosomes | --> embryonic death & cancer malignancy

Question 39

How is chromosome replication initiated?

Answer 39

Multiple origins on each chromosome - each origin fires once per cell cycle = ensures that DNA is copied only once

Question 40

How is chromosome replication timed?

Answer 40

Euchromatin replicated early | Heterochromatin replicated later

Question 41

What are the different changes in chromosome structure called?

Answer 41

``` > deletion > duplication > inversion - paracentric - pericentric > translocation - balanced - unbalanced > dicentric chromosome ```

Question 42

Give an example of fragile regions for chromosomal breaks

Answer 42

TAD boundaries

Question 43

What are the 2 types of leukaemia?

Answer 43

``` ALL = acute lymphoblastic leukaemia AML = acute myeloid leukaemia ```

Question 44

How is leukaemia caused?

Answer 44

1.translocation between chromosome 9 & 22 2. fusion of 2 genes: > BCR = S/T kinase + Rho GEF > ABL1 = NES + NLS 3. = BCR-ABL fusion protein

Question 45

What does the BCR-ABL protein do?

Answer 45

``` Constitutively activate kinase (= always on) = oncogene --> over-proliferation =stem-like state = resistance to cell death ```

Question 46

Which chromosome changes have occurred in human evolution?

Answer 46

Telomere-to-telomere fusion in chromosome 2 (all other primates have 2 chromosomes where we have chromosome 2) Duplication of SRGAP@ --> changes in neurons = sensory perception, memory & language