Chromatin Structure And Histones Code Flashcards
What does chromatin consist of?
DNA + Histones + RNA
Give the definition of chromatin
Nuclear complex of DNA and associated proteins that forms chromosomes within the nucleus of eukaryotic cells
Give the general function of chromatin
Packaging long DNA molecules into more compact and smaller volume to fit into the nucleus and to protect the DNA structure and sequence
What are the four levels of chromatin packaging, how much do they increase packaging and what is the rough size of them
1- nucleosomes- 7fold - 10nm
2- nucleosomes packed into fibres- 6fold- 30nm
3-fibres pack into loops and TADs to form chromatin - 3fold- 100-250nm
4- mitotic chromosome - 700-1000nm
When does chromatin condensation happen?
Prophase
Give the structure and function of euchromatin
Low compactivity (10nm fibre) - beads on a string
Gene rich
Enzyme accessible
Involved in DNA transcription, replication or repair
Give the structure and function of heterochromatin
Highly condensed (30nm) fibre
Darkly staining areas of chromatin often associated with nuclear envelope
Gene poor
Constitutive or facultative
What is constitutive heterochromatin?
Contains highly repetitive sequences of DNA which are genetically inactive and serve as a structural element (in the telomeres and centromeres)- always switched off
What is facultative heterochromatin?
Regions on chromosomes which become heterochromatin in certain cells and tissues- can be turned on/off at any given point in the organisms development or in a certain tissue
How does chromatin show plasticity?
A choice of histone variants, modifications of DNA bases and reversible posttranslational modifications of histone tails
Give the definition of a nucleosome
A little DNA wrapped around histones
What does an octamer core consist of?
H2A, H2B, H3 AND H4 (two of each)
Where are the N-terminal tails in relation to the octamer core?
Outside
How much DNA wraps around the histone cores?
146 base pairs or 1.7 turns of DNA
Where is the H1 protein found?
Wrapped around another 20 base pairs of linking DNA
What is The purpose of a H1 protein?
Stabilises the zigzagged 30nm chromatin fibre?
What happens to the histones each time a polymerase reaches it?
They have to be removed and replaced behind it (having been recycled and resynthesised)
When does a chromatin loop happen?
When stretch’s of genomic sequences that lie on the same chromosome are in close physical proximity to each other
What is cohesion in relation to chromatin loops?
A protein ring that binds to DNA and facilitates loops
What do chromatin loops exist?
They provide a favourable environment for process such as DNA replication, transcription and repair
What is a topologically associated domain (TAD)?
Highly conserved chromatin domain that shape functional chromosomal organisation.
What do TADs do?
We don’t know, but their disruption leads to disease so they must do something
What is a chromosome territory?
A non overlapping domain of the nucleus occupied by uncondensed chromosomes- composed of TADs
What is epigenetics?
Heritable and reversible changes in gene expression which don’t involve a change in the DNA sequence. Results from external or environmental factors or as a part of a development programme
Give some examples of covalent histone modifications
Methylation, acetylation, phosphorylation, ubiquitylation
What happens in histone methylation?
Histone tails are methylated by histone methyltransferases (HMTs) and demethylated by histone demethylases (HDMs)
What are the most common methylations?
Mono, Di, tri of lysines and argenines
What does methylation of lysine residues cause (2 options)?
Chromatin condensation or decondensation
What happens when lysine residues are methylated?
They are more susceptible to transcription factors
What does H3K9me3 stand for?
Histone 3, 9th lysine on that tail, 3 methylations
What is histone acetylation?
Histone tails are acetylated by histone acetyl transferases (HATs) and deacetylase by histone deacetylase (HDACs)
What is most commonly acetylated?
Lysines
What are acylated histones normally associated with?
Relaxed chromatin and gene expression
What are deacylated histones normally associated with?
Closed chromatin and the silencing of genes
What is aberrant acetylation associated with?
Solid tumours and haematological malignancies
What are histone tails phosphorylated and dephosphorylated by?
Histone tails are phosphorylated by protein kinases and dephosphorylated by proteases
Where can histones be phosphorylated?
Serine, threonine and tyrosine
What is the phosphorylation of H3s10 and H3s28 involved in?
Chromatin condensation during mitosis and meiosis as well as chromatin relaxation linked to transcription activation
Where (and using what) does histone ubiquitylation take place?
Ubiquitin ligases and deubiquitinating enzymes. Takes place primarily on lysines of histones H2A and H2B
What is H2Aub more commonly correlated with?
Gene silencing
What is H2Bub more frequently associated with?
Transcription activation
What is a histone code?
Combinations of post-translational modifications on the same or different histone tails
What are histone code readers?
Protein complexes that read combinations of marks
What does a chromodomain specifically recognise? (Histone code readers)
Methylated residues
What does a bromodomain specifically recognise? (Histone code readers)
Bind to acylated residues
