DNA and Chromosome Structure

Question 1

Describe the structure of nucleosomes.

Answer 1

Nucleosome is a repeating unit of DNA wrapped around an octamer of histone proteins.

8 histone proteins compose the histone core (histone octamer).

H2A and H2B associate to form a dimer through ‘the handshake interaction’, same goes for H3 and H4.

2 copies of each protein associate to form the histone octamer.

Question 2

Describe the ‘beads on a string’ structure.

Answer 2

DNA (- charged) wraps itself around histone (+ charged) proteins (nucleosome) with sections of linker DNA in between.

Question 3

Describe the structure of histones.

Answer 3

The tails of the histone protein is not inside the core, but actually exposed.

The N terminals are usually exposed, and therefore modified.

While the C terminals are inserted in the particles for function of DNA.

Question 4

What are the different levels of compaction?

Answer 4

‘Beads on a string’, zig-zag, loops, compaction of loops to heterochromatin, chromosomes

Question 5

What are radial loop domains?

Answer 5

In metaphase chromosomes, highly compact radial loops remain anchored to a scaffold formed from proteins in the nuclear matrix.

Question 6

Describe euchromatin.

Answer 6

Less condensed and capable of gene transcription.

Occupies most chromosomal regions in non-dividing cells.

Question 7

Describe heterochromatin.

Answer 7

Highly compact and transcriptionally inactive.

Occupies some localized regions in nondividing cells.

Question 8

What happens to chromatin before mitosis?

Answer 8

Euchromatin will be converted to heterochromatin.

Question 9

What is constitutive heterochromatin?

Answer 9

Regions that are always found in heterochromatic states.

Question 10

What is facultative heterochromatin?

Answer 10

DNA regions that can switch between heterochromatin and euchromatin states.

Question 11

What are chromodomain proteins?

Answer 11

Chromodomain proteins bind to DNA to keep the heterochromatin state.

Question 12

What regions are always heterochromatic?

Answer 12

Centromeres

Telomeres

Question 13

Describe the localization of chromatin.

Answer 13

Each chromosome has its specific position in distinct and non-overlapping chromosome territories.

Chromatin can move to specific sites within the nucleus to alter gene expression. This happens due to changes of the cell, which happen due to signals.

Question 14

Describe the localization of chromatin.

Answer 14

Each chromosome has its specific position in distinct and non-overlapping chromosome territories.

Chromatin can move to specific sites within the nucleus to alter gene expression. This happens due to changes of the cell, which happen due to signals.

When a set of genes become ‘on’ together, they both go to a specific active location in the nucleus.

Question 15

What are some important histone methylations?

Answer 15

Acetylation, methylation and phosphorylation.

Question 16

How can histones be modified for transcription?

Answer 16

Eukaryotic transcription regulators help initiate transcription by recruiting chromatin modifying proteins.

This changes the state of chromatin to allow transcription, this state is determined by transcription regulators.

Histone acetyltransferase adds acetyl groups to N terminal tail residues. It’s a modifier of the state of chromatin, as well as a component of transcriptional activation complexes.

Question 17

What are histone variants?

Answer 17

Proteins that substitute the core histones nucleosomes and usually grant special structural or functional features.

For example, transcription activation; centromere function and kinetochore assmebly… etc.

Question 18

How do histones have a dynamic structure?

Answer 18

Their changes are catalyzed by ATP - dependant chromatin - remodelling complexes.

Question 19

How do histones have a dynamic structure?

Answer 19

The movement of nucleosomes with DNA is possible due to specific chromatin remodelling complexes which use ATP to catalyze the sliding of nucleosomes around DNA.

Question 20

What is meant by histone having a dynamic structure?

Answer 20

Nucleosomes have a dynamic structure, and are frequently subjected to changes.

The nucleosome is wrapped for a short amount of time before undergoing dynamic modification. Then it can be unwrapped before being rewrapped.

When DNA is less wrapped around histones, it can expose specific sequences. During unwrapping, these sequences can be bound to sequence-specific DNA-binding proteins.

After binding, the proteins become a complex with the nucleosomes and carries out its function.

Question 21

How can histones be changed by proteins?

Answer 21

Negatively charged proteins serve as chaperones by using their state to detach histones from chromatin and replace them with other dimers, using up ATP in the process.

An entire nucleosome can be replaced, or its components by specific remodelling complexes which uses ATP to do its job.

Question 22

What is meant by ‘the histone code’?

Answer 22

The covalent modifications and the histone variants act in concert to produce a ‘histone code’ that helps to determine biological function.

Question 23

Describe chromatin reader complexes.

Answer 23

The histone code must be read by chromatin reader complexes, which reads and interprets this code to transform it into different states of the chromatin.

The complex is generally made by scaffold proteins and other specific proteins which recognize different types of modifications.

Question 24

How do code readers and writer spread chromatin modifications?

Answer 24

A complex of code readers and code writer proteins can spread specific chromatin modifications for long distances along a chromosome.

When a regulatory protein is attempting to bind to DNA, it brings a writer protein, which starts ‘writing’ - adding a modification to a specific N-terminal tail of a histone.

This modification is then read by a reader complex. The complex behaves as a bridge with histone modifying enzymes to spread the modification to consecutive histones.

A wave of chromatin condensation is eventually spread.

Question 25

How is the spreading of chromatin modifications regulated?

Answer 25

Along genomes, specific barrier regions can be found that can stop the spread of chromatin state and separate neighbouring chromatin domains.

Different types of barrier proteins can be found. They can be bound to euchromatin to stop the spreading heterochromatin to euchromatin.

Question 26

How are histones reassembled after mitosis?

Answer 26

This association does not happen spontaneously, specific chaperones proteins are needed to load histones onto growing DNA.

CAF1 loads H3-H4 tetramer into newly synthesised DNA strands. NAP1 loads H2A-H2B dimers onto both newly synthesized and original strands.

This occurs after the replication fork.

Both parental and new histones are used.

Question 27

How can nucleosomes be studied?

Answer 27

Using specific enzymes that can digest DNA, this is isolated from DNA strands.

A high concentration of salt is used to breakdown DNA and proteins, the DNA strand and protein is the nobtained.

Question 28

What are telomeres?

Answer 28

Telomeres are packed into specialized structures that protect the ends of chromosomes.

They are not subject to exonuclease digestion and thus protects eukaryotic chromosomes from digestion.

Different length telomeres are highly regulated. An increasing number of cell divisions (seen as aging) tend to have shortened telomeres.

Question 29

Describe telomerase.

Answer 29

Telomerase is a complex of part RNA and protein.

The end of a chromosome interacts with the active site of telomerase protein as well as the RNA component of telomerase.

A part of the RNA interacts with the chromosome to synthesise telomere DNA.

Question 30

How can chromosomes be coloured?

Answer 30

Chromosomes are each coloured by labelling them with different coloured fluorescent dyes.

Question 31

What are the names for the longer and shorter arms of the chromosome?

Answer 31

P arm for the shorter side and Q for the longer one.