chromatin structure and function

Question 1

what is a chromatin

Answer 1

it is a nuclear complex of DNA and proteins to form chromosomes found in the nucleus of eukaryotic cells

Question 2

what are the functions of chromatin

Answer 2

packaging of long DNA molecules into a denser and more compact shape to fit into the nucleus.

for the protection of the DNA structure and sequence.

Question 3

what are the 4 levels of DNA packaging

Answer 3

nucleosome- beads on a string
30nm fibre
active chromosome
metaphase chromosome

Question 4

When does chromatin start to condense

Answer 4

during prophase and it becomes visible as chromosomes.

Question 5

during interphase what is chromatin organised as

Answer 5

euchromatin and heterochromatin

Question 6

describe the 1st level of DNA packaging

Answer 6

-DNA+histones (nucleosomes) which are made up of double-stranded DNA wrapped around histone proteins.
-increases DNA packaging by 7 fold
-it has approximately 10nm diameter

Question 7

describe the 2nd level of DNA packaging

Answer 7

-nucleosomes pack themselves into fiber
-increases DNA packaging by 7 fold
-it has a diameter of 30nm

Question 8

describe the 3rd level of DNA packaging

Answer 8

-fibers pack themselves into loops and topologically associated domains(TADs) and form chromatin
-increases DNA packaging 3 fold
-has a diameter of 100-250nm

Question 9

describe the 4th level

Answer 9

-it is represented by mitotic chromosomes(only visible during cell division)
-increases DNA packaging by 1000 fold
-it has a diameter of 700-1000nm

Question 10

describe euchromatin

Answer 10

-it is rich in genes.
-has lightly staining areas of chromatin.
-it is accessible to proteins involved in DNA replication and repair and transcription.
-low compacticity chromatin; 10nm fiber “beads in a string”.

Question 11

describe heterochromatin

Answer 11

-highly condensed; 30nm fiber
-gene poor
-it has darkly staining areas of chromatin
-it can be facultative or constitutive.

Question 12

describe constitutive heterochromatin

Answer 12

these are heterochromatin containing highly repetitive sequences of DNA that are genetically inactive and serve as a structural element of a chromosome.

Question 12

describe facultative heterochromatin

Answer 12

this refers to regions of a chromosome that may be uncondensed(become euchromatin) at certain moments of their development. they contain genes that are silenced through different mechanism and these genes can only be expressed at certain moments of person’s life.e.g inactivation of the chromosome X in female mammals

Question 13

describe how chromatin shows elasticity

Answer 13

it can condense and decondense which is enabled by a choice of histone variants, modifications of DNA bases and reversible post-translational modifications (PTM) of histone tails.

Question 14

What are function of TADs

Answer 14

these are highly conserved chromatin domains that shape functional chromosomal associations. their disruption leads to diseases.

Question 15

what are chromosome territories

Answer 15

these are non-overlaping seements of the nucleus that contain uncondensed chromosomes they are composed of TADs.

Question 16

what do histones assemble to form?

Answer 16

an octamer core which is composed of H3H4 tetramer which is flanked by H2A and H2B dimers. it also contains n-terminals which stay outside the octamer core.

Question 17

how many base pairs of DNA wrap around a histone core

Answer 17

146 bp which is 1.7turns of DNA.

Question 18

what is the function of H1 protein

Answer 18

H1 protein acts like a clip that keeps the DNA wrapped around the histone core in place.

Question 19

what is a linker DNA

Answer 19

this is a DNA strand(38-53bp) that links adjacent nucleosomes.it helps to stabilize the zig-zagged 30nm fiber

Question 20

what is the protein loop that binds to DNA and facilitates the formation of loops

Answer 20

cohesin

Question 21

what is epigenetics

Answer 21

these are reversible changes in gene expression that do not involve any changes in DNA sequence. it occurs as a result of environmental factors or external factors or as part of development program

Question 22

what are the 4 types of histone modifications

Answer 22

histone methylation
histone acetylation
histone phosphorylation
histone ubiquitylation

Question 23

features of histone methylation

Answer 23

-histone tails are methylated by histone methyl transferases and demethylated by histone demethylases.
-it can either be mono, di or tri methylation of lysines and arginines
-the methylation of some lysine residues can cause condensation (e.g H3K9me3) while some can lead to decondensation (e.gH3K9me1)

Question 24

features of histone acetylation

Answer 24

• histone tails are acetylated by histone acetyl tranferases and deacetylated by histone deacetylases.
  -most common is the acetylation of lysines.
  -acetylated histones are usually associated with relaxed chromatin and gene expression while deacetylated histones are usually associated with closed chromatin and gene silencing.
  -aberrant acetylation is usually associated with tumors and hematological malignancies

Question 25

what are features of histone phosphorylation

Answer 25

-histone tails are phosphorylated by protein kinases and dephosphorylated by proteases.
-it can occur on serine, threonine and tyrosine residues
-Phosphorylation of H3S10 and H3S28 is
involved in chromatin condensation during
mitosis and meiosis, as well as in chromatin
relaxation linked to transcription activation.

Question 26

what are features of protein ubiquitylation

Answer 26

-histone tails are ubiquitinated by ligases and deubiquitinated by deubiquitinating enzymes
-usually occurs on lysines of H2A and H2B histones.
-H2Aub is associated with gene silencing while H2Bub is associated with transcription activation.

Question 27

what is the histone code

Answer 27

this is the combination of post-translational modifications on the same histone tails.

Question 28

what are code readers

Answer 28

protein complexes that
read combinations of marks:
chromodomains specifically recognize
methylated residues, while
bromodomains bind acetylated
residues. This read leads to chromatin
remodelling (open or close).