[W3] Genome Organisation-2

Question 1

Why does DNA need to be packaged in cells?

Answer 1

DNA is extremely long and must be compacted to fit into the cell nucleus without tangling or damage.

Question 2

What is the packing ratio?

Answer 2

The packing ratio is the length of DNA divided by the length into which it is packaged.

Question 3

Give an example of a human chromosome’s packing ratio.

Answer 3

Chromosome with 14,000 μm DNA is packed into 2 μm → packing ratio = 7000.

Question 4

What is a nucleosome?

Answer 4

The basic unit of chromatin; 147 bp of DNA wrapped around a histone octamer.

Question 5

Which histones make up the nucleosome core?

Answer 5

2 copies each of H2A, H2B, H3, and H4.

Question 6

What is the role of histone H1?

Answer 6

Binds to linker DNA between nucleosomes to promote higher-order folding.

Question 7

Name 4 types of histone modifications.

Answer 7

• Acetylation
• Methylation
• Phosphorylation
• Ubiquitination

Question 8

What does histone acetylation generally lead to?

Answer 8

Loosens chromatin structure and increases transcription.

Question 9

What is the ‘histone code’?

Answer 9

The idea that specific combinations of histone modifications influence chromatin function and gene regulation.

Question 10

What are the three structural levels of chromatin?

Answer 10

• Primary: 11 nm fiber (nucleosome chain)
• Secondary: 30 nm fiber (solenoid or zigzag)
• Tertiary: Looped domains (~85 kb)

Question 11

What attaches chromatin loops to the nuclear matrix?

Answer 11

Matrix Attachment Regions (MARs).

Question 12

Which is transcriptionally active: euchromatin or heterochromatin?

Answer 12

Euchromatin.

Question 13

Where is heterochromatin usually located?

Answer 13

At centromeres, telomeres, and other gene-poor regions.

Question 14

When is euchromatin replicated?

Answer 14

Throughout S-phase.

Question 15

When is heterochromatin replicated?

Answer 15

Late S-phase.

Question 16

Which type of chromatin recombines more frequently?

Answer 16

Euchromatin.

Question 17

What is a chromosome?

Answer 17

A discrete unit of DNA and proteins carrying many genes; visible during cell division.

Question 18

What are the key parts of a chromosome?

Answer 18

• Centromere
• Telomeres
• Short arm (p)
• Long arm (q)
• Chromatid

Question 19

What is the function of the centromere?

Answer 19

Ensures proper segregation of chromosomes during mitosis/meiosis; attaches to spindle.

Question 20

What type of DNA is found near centromeres?

Answer 20

Satellite DNA – highly repetitive, non-coding sequences.

Question 21

What is a telomere?

Answer 21

Repetitive DNA sequence at chromosome ends that protects them from degradation.

Question 22

What is the human telomere sequence?

Answer 22

TTAGGG.

Question 23

What is the role of the shelterin complex?

Answer 23

Protects telomeres and recruits telomerase for extension.

Question 24

What is telomerase?

Answer 24

A ribonucleoprotein enzyme that extends telomeres using an RNA template.

Question 25

In which cells is telomerase active?

Answer 25

Actively dividing cells (e.g. stem cells, cancer cells); not in quiescent cells.

Question 26

What happens if telomerase is inactive?

Answer 26

Telomeres shorten with each division, leading to cell senescence.

Question 27

What is a chromosome territory?

Answer 27

A discrete 3D space occupied by each chromosome in the interphase nucleus.

Question 28

What is FISH and what does it do?

Answer 28

Fluorescent in situ hybridisation; visualises specific DNA sequences in cells.

Question 29

What does chromatin looping do?

Answer 29

Brings distant enhancers and promoters together to regulate gene expression.

Question 30

Which proteins mediate chromatin loops?

Answer 30

CTCF and cohesin.

Question 31

What is the loop extrusion model?

Answer 31

Cohesin extrudes DNA into loops until it reaches CTCF-bound sites, forming regulatory domains.

Question 32

What is a TAD?

Answer 32

Topologically Associating Domain – a self-interacting chromatin region (~1–2 Mb).

Question 33

What defines TAD boundaries?

Answer 33

CTCF and insulator elements.

Question 34

What are LADs?

Answer 34

Lamina-associated domains; gene-poor regions attached to the nuclear lamina.

Question 35

What are NADs?

Answer 35

Nucleolar-associated domains; associate with nucleoli and rRNA synthesis regions.

Question 36

What is an insulator?

Answer 36

A DNA element that blocks interaction between enhancers/silencers and promoters, and defines chromatin domains.

Question 37

What is a transcription factory?

Answer 37

A subnuclear space where multiple active genes cluster to be co-transcribed.

Question 38

What is CTCF?

Answer 38

A zinc finger DNA-binding protein that regulates chromatin looping and defines TAD borders.

Question 39

What is the cohesin complex made of?

Answer 39

SMC1, SMC3, STAG1/2, and RAD21; forms a ring around DNA to hold loops.

Question 40

What is the 3C technique?

Answer 40

Chromosome conformation capture; identifies physical interactions between chromatin regions.

Question 41

Where are most disease-associated variants located?

Answer 41

In non-coding DNA regions like enhancers.

Question 42

How does 3D genome misfolding lead to disease?

Answer 42

Disruption of enhancer-promoter loops or TAD boundaries causes gene misregulation.

Question 43

What can happen if a TAD boundary is broken?

Answer 43

Enhancers may activate the wrong genes, leading to disease.