Week 5 - Chromatin Structure Regulation Flashcards
Why is the DNA packaged inside the nucleus?
- protection from damage
- regulate its metabolism
What is chromatin?
- subunit structure nucleosome repeating unit
- levels of organisation to form chromosomes
- levels vary depending on whether cell is in interphase or mitosis or meiosis
What is the structure of the nucleosome?
- 2 molecules each of the 4 core histones
- each histone dimer has 6 DNA binding surfaces
- histone octamer organises into helical turn
- packaged into disc
What are the two types of chromatin?
heterochromatin
- highly condensed
- inactive genes
- positive N terminal of histone binding to DNA
euchromatin
- extended
- active genes
What is the first level organisation structure of chromosomes?
11nm fibril
- DNA wrapped
- turns outside of flat disc of histone proteins
- each bead is a nucleosome
- nucleosome joined to neighbour by linker DNA
- 6-fold reduction (6 packing ratio)
- present in both hetero/eu chromatin
- active form
- low salt, DNA, four histone pairs to assemble in vitro
What is the second level organisation structure of chromosomes?
- 30nm fibre
- left handed solenoid helix
- 6 nucleosomes per turn
- 400 packing ratio
- H1 histone required
- transcription is inactive
- during interphase and mitosis/meiosis
- high salt solution, DNA, all histone species to assemble
What is the third level organisation structure of chromosomes?
- loops
- rosettes: 6 loops
- coils: 30 rosettes
- 10000 packing ratio
- heterochromatin
What is the fourth level organisation structure of chromosomes?
- chromatids
- maximally condensed in mitosis
- > 10000 packing ratio
- 5 µm length
What is chromatin remodelling?
- ATP-dependent chromatin remodelling complexes
- alter/ slide/ displace nucleosomes
- exchange one histone for another
What are histone post-translational modifications?
- methylation/demethylation
- acetylation/deacetylation
- phosphorylation/dephosphorylation
- modifications mutually exclusive
- cannot methylate lysines (inactivate) if already acetylated (activate)
- reversible
What is epigenetics?
- gene expressions states
- stable over rounds of cell division
- not involve changes in DNA sequence
- for development
- inheritance
- disease / cancer/ ageing
How is transcription regulated by histone modification?
- opens or closes up the DNA for access
- domains can read the histone modifications to silence or activate transcription
- based on the modification and amino acid
How is methylation regulated by metabolites?
- regulated by methyltransferase
- and demythylases
- regulated by S-AdenosylMethionine (SAM)
- as methyl donor
- synthesised by methionine and ATP
- by Methionine AdenosylTransferases (MATs)
- S-AdenosylHomocysteine (SAH) also produced
- inhibitor of methyletransferases
- SAM:SAH ratio
How is demethylation regulated by metabolites?
- demethylases use metabolites as cofactors
- α-KG induces demethylation using dioxygenation
- inhibited by metabolites structurally related to α-KG
