7. Chromatin structure and Histone code

Question 1

Describe Chromatin (4pts)

Answer 1

1. Chromatin is the nuclear complex of DNA and associated proteins that form chromosomes within the nucleus of eukaryotic cells.
2. DNA+Histones+Rna= Chromatin
3. Chromatin function= Packaging long DNA molecules into a more compact and denser shape to fit into the nucleus and to protect the DNA structure and sequence. This allows for processes such as mitosis.
4. There are 4 levels of packaging.

Question 2

Describe Level 1 (3pts)

Answer 2

1. DNA and histones combine to form nucleosomes
2. Increases DNA packaging 7 fold
3. size of the structure= approximately 10nm

Question 3

Describe level 2 (4pts)

Answer 3

1. The nucleosomes pack themslves into fibres
2. Increases DNA packaging 6 fold
3. Contains less active genes
4. 30nm

Question 4

Describe level 3 (3pts)

Answer 4

1. 30 nm fibres pack themselves into loops and TAD’s and form chromatin
2. Increases DNA packaging 3 fold
3. 100-250 nm

Question 5

Describe level 4 (4pts)

Answer 5

1. Chromosomes only visible in mitosis
2. Representd by the mitotic chromosome
3. Means 100 fold-packaging
4. 700-1000nm

Question 6

When does Chromatin condensation begin (1pt)

Answer 6

Chromatin condensation begins during prophase and chromosomes become visible

Question 7

How is chromatin organised in interphase (1pt)

Answer 7

In interphase chromatin is organised in euchromatin and heterochromatin. During interphase you wont be able to see chromosomes only chromatin.

Question 8

Describe Euchromatin (5pts)

Answer 8

1. Low compactictiy
2. Described as beads on a string
3. Areas that are rich in genes
4. Lightly staining areas of chromatin
5. Euchromatin is accessible to the enzymes involved in DNA transcription, replication or repair.

Question 9

Describe Heterochromatin (5pts)

Answer 9

1. Represents 10% of the whole chromatin
2. Highly condensed, 30 nm fibres
3. Dark staining areas of chromatin often associated with the nuclear envelope
4. Lacking in genes
5. constitutive or facultative

Question 9

Describe Heterochromatin (5pts)

Answer 9

1. Represents 10% of the whole chromatin
2. Highly condensed, 30 nm fibres
3. Dark staining areas of chromatin often associated with the nuclear envelope
4. Lacking in genes
5. constitutive or facultative

Question 10

Describe Constitutive heterochromatin (1pts)

Answer 10

Invariable heterochromatin containing highly repetitive sequences of DNA which are genetically inactive and serves as a structural element of the chromosomes.

Question 11

Describe Facultative heterochromatin (1pts)

Answer 11

Regions of chromosomes that become heterochromatin in certain cells and tissues. It inactivates X chromosome in female somatic cells. Contains genes that can be activated at some point in their development.

Question 12

How does chromatin show plasticity (1pts)

Answer 12

Plasticity is the quality of being easily shaped or moulded. Chromatin shows plasticity enabled by choicer of histone variants, modification of DNA bases such as methylation of nucleotides and reversible post translational modifications of histone tails.

Question 13

Describe Histones (1pt)

Answer 13

Histones are the main proteins in chromatin whose function is packaging DNA into nucleosomes

Question 14

Describe nucleosomes (6pts)

Answer 14

1. The first level of chromatin packaging is the nucleosome
2. Nucleosomes are the fundamental structural unit of chromatin. They are composed of a little DNA wrapped around proteins called histones.
3. Histones assemble to form an octamer core. 146 base pairs of DNA wrap around the histone core to form a nucleosome.
4. Nucleosomes are joined by linker DNA (20 base pairs) that runs between them.
5. Long chains of nucleosomes give the appearance of beads on a string.
6. Nucleosomes tightly pack together into a fibre of 30nm.

Question 15

Describe Chromatin Loops (3pts)

Answer 15

1. Chromatin loop formation= Chromatin looping occurs when stretches of genomic sequences that lie on the same chromosome are in close physical proximity to each other.
2. Cohesion is the protein ring that binds to DNA and facilitates loops.
   3, Chromatin loops provide a favourable environment to processes such as DNA replication, transcription and repair.

Question 16

Describe TADS (1pts)

Answer 16

Topologically associated domains are highly conserved chromatin domains that shape functional chromosomal organisation. Their function is not fully understood however their disruption leads to disease.

Question 17

Describe Chromosome territories (1pt)

Answer 17

Chromosome territories are non overlapping regions of the nucleus occupied by uncondensed chromosomes. They are composed of TAD’s.

Question 18

Describe epigenetics (2pts)

Answer 18

1. Epigenetic’s= Heritable and reversible changes in gene expression which do not involve a change in the DNA sequence.
2. Results from external or environmental factors or as part of a development program.
3. examples- DNA methylation, covalent histone modification

Question 19

Describe Histone modifications (2pts)

Answer 19

1. Histone modifications control the accessibility of the chromatin transcriptions activities.
2. There are 4 types:
3. Histone methylation
4. Histone acetylation
5. Histone phosphorylation
6. Histone ubiquitylation

Question 20

Describe Histone methylation (5pts)

Answer 20

1. Histone tails are methylated by HMT’s and demethylated by HDM’s.
2. HMT’s convert Heterochromatin to Euchromatin.
3. HDM’s convert Euchromatin to Heterochromatin.
4. Methylation of some lysine residues cause chromatin condensation. It is more accessible to transcription factors and therefore open to gene transcripts.
5. Methylation of other lysine residues cause chromatin decondensation.

Question 21

Describe Histone Acetylation (4pts)

Answer 21

1. Histone tails are activated by HAT’s and deacylated by HDAC’s.
2. Most common= acetylation of lysine
3. Acylated histones= relaxed chromatin and gene expression.
4. Deacylated histones= closed chromatin and silencing of genes.

Question 22

Describe Histone Phosphorylation (3pts)

Answer 22

1. Histone tails are phosphorylated by protein kinases and dephosphorlayted by proteases.
2. Can occur on serines, threonine and tryosine
3. Phosphorylayion of H3S10 + H3S28= chromatin condensation during mitosis and meiosis, chromatin relaxation linked to transcription activation.

Question 23

Describe Histoner ubiquitylation (3pts)

Answer 23

1. Ubiuqtin ligases and debiquting enzymes
2. Primarily on lysine of histones H2A and H2B
3. H2AUB = more frequently correlated with gene silencing
4. H2Bub= transcription activation

Question 24

Describe the Histone code (1pts)

Answer 24

Combination of post-translational modification on the same or different histone tails.

Question 25

Describe code readers (1pts)

Answer 25

Code readers are protein complexes that read combination of marks. Chromodomains specifically recognise methylated residues while bromodomains bind acetylated residues. This read leads to chromatin remodelling.