Lecture 6 : Histones and Packaging Flashcards
What is the DNA package heirarchy?
Amino acids → Histones → Nucleosome → Chromatin → Chromosomes → Nucleus
What is the nucleosome?
- Basic unit of chromatin
- Made from 2 pairs of the 4 core histones H2A, H2B, H3 and H4, so 8 histones all together
- Forms octameric core
- DNA coils tightly around nucleosome
Histones H3 and H4
- Form a histone handshake motif
- Stabilises nucleosome
Histones H2A and H2B
- Form a dimer
- H2A : H2B dimers bind above and below H3 : H4 tetramer, forming the octamer
Variants of H2A
H2A.Z
- Alters canonical nucleosome
- Changes interaction stability between H2A and H2B
H3 variants
H3.1, H3.2, CenpA and H3/It
Level 1 - Nucleosome
2 H3:H4 complexes bind in a handshake motif to form a tetramer complex. H2A and H2B dimers bind above and below the tetramer to form an octamer. DNA, of length 146 base pairs, coils tightly around the octamer in a left handed superhelix, where the DNA path is approximately 1.8 superhelical turns. DNA does NOT form a smooth path around nucleosome. The accessibility of nucleases is restricted.
Level 2 - 10nm Fibre
The 10nm fibre looks like ‘beads on a string’. It consists of a string of nucleosomes (everything contained in level one), where each nucleosome is connected by ‘strings’ of linker DNA, which is in its double helix form.
Packing ratio 6-7
Level 3 - 30nm Solenoid
Nucleosomes in 10nm fibre coil and fold into a more compact, helical (solenoid) structure, containing roughly 6 nucleosomes per turn. Has a diameter of 30nm. H1 is critical in this structure, because it binds to linker DNA between nucleosomes, helping to stabilise interactions between adjacent nucleosomes. Therefore it aids in compaction.
Packing ratio - 40
Level 4 - 300nm Solenoid
Each loop contains 60-100kb of DNA tethered by non-histone scaffold proteins.
Packing ratio - 680
Level 5 - 700nm Fibre
A coiled coil, requires loops of chromatin to coil again forming condensed 700nm fibre
Packing ratio - 10^4
Level 6 - Metaphase Chromosome
Little unfinished