Chromatin And Gene Expression Flashcards
How do we have so many types of cells with the each having the same genetic material?
- via turning gene on and off
- having unique gene pattern
- same info can be used in different ways
- epigenetic modification (in response to environmental stress)
Ways of Silencing a gene
Temporary - Histone methylation* - depends, can also activate gene (normally H3K9/27)
Permanently - DNA methylation
Levels of gene expression control
- Transcriptional level (rate limiting and most important)
- RNA processing control (splicing, adding caps/tails)
- Export/ localisation control
- Translational control - ribosomal
- PTM - e.g. MicroRNA
Define genes
Genes are transcriptional units that are composed of structural and functional info coding for a protein and regulatory element, respectively
Promoter
Essential in initiating transcription at LOW level
Positioned just upstream of target gene and is where RNA pol II binds
Enhancers
Enhancers are regulatory DNA sequences that can be found upstream, downstream or even within the gene and allows FINE TUNING of gene expression. They often respond to external signals
Types of PTM and what they do on histone tail and DNA
- Acetylation - loosen chromatin (activate gene transcription)
- Methylation - if histone then can activate or silence gene. If on DNA - permanently silent gene (no known DMT in specialised cell)
- Phosphorylation
- ADP-ribosylation - cross talk between PTM and core histone
- Ubiquitination - allow crosstalk with another histone modification
Regulatory elements often LACK nucleosomes - why?
More accessible for TF to bind
Nucleosome composition
H1 linker + 2(H2A+H2B +H3+H4)
Function and characteristics of histone N’ tail
Highly flexible and one of the most modified structure
Unstructured - no fixed structure within cell
Interact with DNA and can alter DNA path around the nucleosome
Great PTM site to fine tune gene expression
Acetylation of histone occurs on what type of residue?
e- amino acids (e.g. Lysine, arginine) at the N term of ALL4 core histones
Order of histone acetylation in lysine
H4 - K16 / K12 or K8 / K5 (‘K16-4-4(-4+1)’)
H3 - K18 / k23/ k14 / k9 / k27 (‘1823-149-27’)
Histone methylation sites
H3 K4/9/27 - K4 (Active)
H4 K20
H1 K26
Normally tri.me.
Permanently silencing a gene requires
Tri me. H3 K9/27
DNA methylation
H3K27 binds to PRC2 (PcG) which contains EZH2, EZH2 binds to H3K27 and permanently silence gene. PRC1 then ubiquitinate H2A to mark cell as permanently off
What is ontology
Ontology defines the function of a gene and it’s functional relationship as well as interaction with other genes. (Which can be mapped out in a list