Genome Stuffz

Question 1

Chromosome

Answer 1

A discrete unit of genome which carries many genes

Each chromosome consists of a very long molecule of duplex DNA + an approximately equal mass of proteins

Question 2

Chromatin

Answer 2

The state of nuclear DNA + it’s associated proteins
Euchromatin - Mostly decondensed form of DNA
Heterochromatin - Tightly condensed form of DNA

Question 3

Nucleosome

Answer 3

A cylinder with DNA organised into ~1.7 turns around the surface
Contains an octane of histones around which DNA winds up
Length of DNA on nucleosome: 146-260bp
Consists of up to 8 histones + 200bp (= 130kDa, 67nm)
Not randomly positioned in DNA, their positions are critical for gene expression + most DNA related processes

Question 4

Difference between chromatin and chromosomes

Answer 4

Chromosomes are more condensed than chromatins

Question 5

Nucleosome organisation patterns in silent vs active chromatin state

Answer 5

Around transcription start sites of silent genes
+ Highly uniformly spaced nucleosome
+ Large variation in positioning across different cells
Around transcription start sites of active genes
+ Heterogeneously spaced nucleosome
+ Little variation in positioning across different cells

Found through single-cell micrococcal nuclease sequencing (scMNase-seq)

Question 6

Linker histone

Answer 6

Made of Histone-1 (H1) variants
H1 can interact with DNA at entry/exit site of nucleosome as well as the central DNA
Stabilises the wrapping of DNA around nucleosome, HQ association with nucleosome facilitates winding of 2 full turns of DNA
Promotes folding +assembly of higher order chromatin structures
Influences nucleosome spacing + involved in regulation of gene expression

Question 7

Linker histone

Answer 7

Made of Histone-1 (H1) variants
H1 can interact with DNA at entry/exit site of nucleosome as well as the central DNA
Stabilises the wrapping of DNA around nucleosome, HQ association with nucleosome facilitates winding of 2 full turns of DNA
Promotes folding +assembly of higher order chromatin structures
Influences nucleosome spacing + involved in regulation of gene expression

Question 8

Flexible histone tails

Answer 8

Flexible histone tails projecting out of nucleosome core contains sites for covalent modifications

Question 9

Post-transaltional modification of histones

Answer 9

Histones can be reversibly covalently modified on their tails by
\+ Methylation
\+ Acetylation
\+ Phosphorylation
\+ Ubiquitation
\+ Sumoylation
\+ ADP-ribosylation
\+ Among other processes
Often reversible + can be maintained through several cell divisions + can change histone protein charges + function of histone octamer

Question 10

Histone code

Answer 10

Combination of all histone modifications that act cooperatively to define structure + function
Correlates with distinct chromosomal states that regulate access to DNA, thereby regulate replication/transcription
Histone modifying enzymes are sorted into 2 types: Erasers ie deacetylase + Writers ie Methyl transferase
Histone code readers are non-histone proteins interacting with the modification of histones

Question 11

Roles of histone modifications

Answer 11

Replication
Transcription 
Histone deposition of DNA
Recombination
DNA repair
DNA methylation