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GTS351 Theme 2 summary
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Full summary of theme 2 (structure of chromatin) made using lecture notes, the textbook and class notes.
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Structure of ChromatinEukaryotic gene control is more complex
- Prokaryotes
- Genes are generally ON by default and have to be repressed to
switch them off
- Cells do not commit to a differentiated state
- Long-term regulatory processes (e.g. chromatin state) are less
influential
- Eukaryotes
- Most genes are OFF by default and need activating factors to
activate transcription
- Since most eukaryotes are multicellular, cell lineages commit to a
differentiation state early on
- There is a complex interplay between short-term transcriptional
responses and long-term regulatory programmes
Short and long-term regulation in eukaryotes
- Short term (reversible)
- Regulatory events quickly turn gene sets on or off in response to
environmental changes e.g. hormones, stress etc
- Proteins interact transiently with DNA control elements
- Transient changes in chromatin structure
- Long term (semi-irreversible)
- Are associated with cell determination, differentiation and more
generally, embryonic development
- Cells are “committed” to a particular cell type - once committed
the cell type shows stability and there is no change to another
type
- Long term changes differ substantially between cell types
- Permanent changes in chromatin conformation occur
- DNA methylation is semi-reversible
Activation of gene expression depends on
- Chromatin conformation that is accessible
- DNA is either tightly or loosely packaged - determines how
accessible DNA control elements are to regulatory proteins
- Chromatin structure can be altered by chemical modifications to
DNA and/or histones and binding proteins or RNA molecules
- Control elements present on DNA
- There is a large variety - basal promoter, enhancers, silencers etc
- Different control regions in combination with different TFs
provide specificity
- Transcription factors (TFs)
- Are proteins that interact with DNA control elements
- Interact with other TFs as well as co-factors
- Interact with RNA polymerases
,Questions regarding chromatin structure and gene regulation
- How is active chromatin packaged before and after transcription of a
gene?
- How are genes in the committed stage packaged?
- What is the role of DNA methylation etc in gene regulation?
- What is the role of histone modifications?
- What is the role of small mRNAs?
Nucleosome: basic unit of chromatin
- 2m of DNA fits into a 10µm nucleus dues to DNA packaging into
chromatin
- 200bp of DNA is wrapped around a histone octamer
- Two molecules of each core histone H2A, H2B, H3 and H4
- 146bp fits roughly 2 turns around a histone and the rest is a linker where
the DNA binds
- There are 5 types of histone proteins
- They have a strong positive charge that neutralises the negative charge
on DNA and allows folding
- First order structure of chromatin
- 2nm double helix DNA is packaged to 10nm fiber - “beads on a
string”
- In the presence of H1 it is more tightly packaged
- In the absence of H1 it is less tightly packaged
, Nucleosome structure and position can be altered
- Achieved through chromatin remodelling
- The nucleosome is highly dynamic - DNA is constantly unwrapping and
rewrapping itself around the nucleosome
- The process involves protein complexes called chromatin remodelling
complexes (CRCs)
- Local chromatin structure differs between regions of DNA
Chromatin remodelling complexes
- CRCs are complexes of proteins that bring about changes in chromatin
compaction
- CRCs can act as either activating or repressing complexes
- CRCs disrupt DNA-histone interactions
- Effect of chromatin remodelling on nucleosomes
- Nucleosome structure changes - DNA is more exposed
- Nucleosome is displaced along the DNA - it moves
- Nucleosome completely disassembles - is lost from the DNA
(nucleosome eviction)
- This causes the chromatin to be more densely or more loosely
packaged i.e. DNA is more/less accessible to regulatory molecules
- CRCs can also exchange histone subunits within the nucleosome -
existing histones can be exchanged with variant forms
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