Chromatin and Chromatin Remodelling Flashcards
(23 cards)
Why is chromatin necessary?
It compacts DNA to fit inside the eukaryotic nucleus using histone proteins
What is chromatin composed of?
DNA + histone proteins, forming a highly ordered structure
What is a nucleosome?
The basic building bock of chirmatin, conisisting of 200 bp of DNA wrapped around a histone octamer
What proteins make up the histone octamer?
2 H2A-H2B dimers
1 H3-H4 tetramer
How does DNA interact with histones in nucleosomes?
DNA coils twice around the histone octamer (146 bp per nucleosome)
Linker DNA (8-114 bp) separates nucleosomes
What conformation do histones and DNA form?
Beads-on-a-string (11nm filament), with histone H1 stabalising nucleosomes
What is the higher-order chromatin structure?
11nm filament folds into a 30 nm chromatin fiber
Further folding leads to the chromatid structure of chromosomes
What are the two main types of chromatin?
Euchromatin - Active, accessible or transcription
Heterochromatin - Inactive, condensed and transcriptionally
What is chromatin remodelling?
The ATP-dependent reorganisation of nucleosomes required for gene activation
How do chromatin remodelling complexes function?
Use ATP hydrolysis to move nucleosomes
Induce sliding, adjustment, or displacement of nucleosomes
What recruits remodelling complexes to promoters?
Sequence-specific activators from teh transcription apparatus
What is teh SWI/SNF complex?
First discovered chromatin remodelling complex in yeast
Controls expression of 2% of all yeast genes
Works by twisting DNA, sliding nucleosomes, or ejecting histones
What is the link between SWI/SNF mutations and cancer?
Found in 19% of tumors, approaching TP53 mutation frequency (25%)
What are the major types of histone modifications? (4 types)
1 - Acetylation
2 - Methylation
3 - Phosphorylation
4 - Ubiquitination
How does histone acetylation affect transcription?
Histome acetyltransferases (HATs) add acetyl groups to lysine residues
Neutralises histone positive charge, reducing its interaction with negatively charged DNA
Opens chromatin structure, increasing transcriptional activity
How does histone deacetylation affect the X chromosome?
Histone H4 is hypo-acetylated on the inactive X chromosome
Leads to formation of Barr bodies (condensed, inactive X chromosomes)
Example - Calico cat cooat colour, results from random X inactivation
What does histone methylation do?
Adds methyl groups to lysine residues, which can either activate or respress transcription
How does heterochromatin form via histone methylation?
H3K9 trimethylation recruits heterochromatin Protein 1 (HP1)
HP1 packs chromatin into a repressive state, silencing genes
Example, Drosophila white gene regulation (red vs. white eye colour)
What is Position Effect Variegation (PEV)?
Random spread of heterochromatin, leading to variable gene silencing in cells
What determines chromatin’s open or closed state?
A combinatoral pattern of histone modifications, regulated by:
- Writers - Add marks (methylases, acetylases)
- Erasers - Remove marks (deacetylases demethylases)
- Readers - Recognise marks (HP1 for heterochromatin formation)
How does chromatin status influence transcription?
Euchromatin (open) is permissive for transcription
Heterochromatin (closed) represses gene expression
Certain transcription factors can actively open closed chromatin
How do promoters become transcriptionally active?
Chromatin remodelling exposes DNA regions
Acetylation and methylation modify histone at promoters
Pioneer trancription factors (TFs) bind closed chromatin and recruit remodelling complexes
What are pioneer TFs?
Proteins that bind closed chromatin, recruiting histone modifiers to open up transcription sites
Example: Oct4 and Sox2 - Critical for pluripotent stem cell formation
