Lecture 3 - Chromosome Epigenetics Flashcards
What is epigenetics?
The difference of trains whether that be due to external or internal ques
Is differentiation a epigenetic process or a genetic one?
epigenetics
What is epigenetic memory?
Ensures all cell types are locked into their specific cell type
Where is epigenetic information found?
The epigenome
What are DNA modifications specific to and what does this allow them to do?
Each cell type and they do this by turning on some genes and not the other
What is the basic package of chromatic?
Nucleosome
What is chromatin?
An assembly of proteins and dna
What happens if chromatin is closed and inaccessible?
The gene is silenced
What happens if chromatin is open and accessible?
The gene can be translated
What is the Histone code hypothesis?
That gene regulation is partly dependent on Histone modifications
What is constitutive heterochromatin?
Closed chromatin which is gene poor and gene indicative.
It replicates in late s phase
What is euchromatin?
Accessible chromatin which means dna can be activated
What is facilitate heterochromatin?
This is where genes are silenced not inactivated this means that in different cell types and epigenomes these can be turned on
What protein holds topical associating domains and nano domains which are both found in chromatin together?
Cohesins
How does dna form Nucleosome (which makes chromatin)
Wrapped around the Histone octamer
After Nucleosome are made they come together in clutches or what?
Nanodomians
Tads come together to make compartments a and b. What does compatment a contain?
Active chromatin
Tads come together to make compartments A and B what does compartment B contain?
Heterochromatin
What is the chromatosome?
A linker Histone has bound to the Nucleosome centre and wraps the DNA more
What does adding the linker Histone do?
Make it less accessible
What part of the core histones are targets for post translational modifications?
The n- and c- terminal
What does post translational modifying histones do to the DNA?
Can drive the opening and closing of chromatin and therefore turning genes on or off
What modifications can happen to the histones tail?
Acetylation, methylation, phosphorylation or ubiquitination
Where do most post translational modifications occur on the tails?
N-terminal
What are Histone writers, readers and erasers?
Proteins or enzymes which add a modification to a Histone
What is an example of a Histone writer?
Histone acetaltransferase which adds an acetyl
What do Histone readers specifically do?
Read the Histone code and so bind to modified parts of it
What do Histone erasers do?
Erase any Histone modifications
Do Histone writers, erasers and readers bind to Dna directly?
No they are recruited by transcription factors at enhancers or promotors
What does Histone acwtylation indicate?
Gene activations
What is Histone acetylation regulated by?
Histone acetyltransferase (HATS - writers) and Histone deacetylases (HDACs - erasers)
What does Histone acetylation do to lysine?
Neutralises it’s positive charge leaving a weak interaction with the phosphate backbone and therefore looser chromatin triggering transcription
What does Histone methylation do?
Histone methylation - writer
Histone demethylase - eraser
Activates or deactivates genes drowning in context
What does H3K4me3 do?
Activation
What is H3K9?
Heterochromatin marker
How does ChIP work?
Fraction chromatin by signification into Nucleosome and put a specific antibody against it. This attaches to bead and is pulled down by centrifugation
Purify DNA and identify DNA based in Histone modification
What does lysine acetylation of H3 and H4 tails correlate with?
Gene activation
Where does the kinetochore attach the chromosomes to?
Spindle fibres
What do centromeres contain?
CENP-A histone and pericentromeric heterochromatin
What is CENP-A the variant histone of?
H3
Does CENP-A and H3 have different N-terminals?
Yes
Is centromere CENP-A conserved across species?
Yes
What are point centromeres?
Centromeres with only CENP-A and nothing else
Position effect Variegation in drosophila - what happens if chromosomal inversion causes the gene to be close to the heterochromatin?
The gene is turned off
Can epigenetic silencing due to position of the gene near heterochromatin be inherited?
Yes
what colour of eyes do drosophila have if they have the W+ gene?
red
What does the one Su(var) gene do to heterochromatin?
Less heterochromatin can form
What does three copies of the Su(var) gene do to heterochromatin?
Cause lots of heterochromatin formation
If drosophila have white eyes what has happened to the heterochromatin?
It has spread lots
What does Suvar bind to to stop heterochromatin spread?
H3K9
What is the second component of the epigenetic code?
DNA methylation
How does DNA methylation work? And what is it known as?
Methyl group is added to a cytosine before a guanine in a 5’ to 3’ section - this is known as CpG dinucleotides
Where are CpG islands located?
Around transcriptional start sites
What are regions of high CpG density?
Hypermethylated = open chromatin
What is H3K4me3 in terms of open or shut chromatin?
Open
What type of methylation is in areas of low CpG density?
Highly methylated
Is a region of high methylation got heterochromatin?
Yes
what would reducing DNA methylation do to repressed genes?
They would be expressed
The status of what maintains active or inactive states via chromatin modification?
DNA methylation
What does Methyl-CpG recognise on proteins?
Methyl DNA binding domains
what does the methyl DNA Binding domain recruit after methyl-CpG is bound?
Chromatin repressor complexes
Is unmethylated CpG recognised by different proteins? What do they recruit?
Yes and these recruit chromatin activating complexes
How does methyl-CpG condense chromatin?
Recruits structures such as a HDAC
What specifically is a reader which binds to the unmethylated CpG island to act as transcriptional factors to recruit chromatin activating complexes?
cfp1
What controls gene dosage?
DNA methylation
Why does x inactivation happen?
The X chromosome is so large compared to the y so when passed on it would cause genetic inequality
In early development we inactive an X chromosome. How do we do this?
We package one of the X chromosomes into facilitate heterochromatin
what is the name of the bundled X chromosome and the facultative heterochromatin?
The Barr body
What is created for dosage compensation?
The Barr body
Is the inactive X chromosome chosen at random?
Yes
what maintains the Barr body?
All clonal descendent cells.
What is necessary and sufficient for x-inactivation?
The x-inactivation centre (XIC)
What gene is transcribed from the inactive x but not the active x gene?
XIST - (inactive x-specific transcripts)
What is the product of the XIST gene?
Non-coding RNA
Where does the non-coding XIST gene remain associated with?
The inactive X chromosome in the female interphase nuclei
What genes lie within the xic?
Brx - Brian x-linked
Tsx -testis x-linked
Cdx4 - caudal-4
CpG islands are usually unmethylated. Is this true in CpG islands in the x-chromosomes?
No they are methylated
Is XIST active?
No
When silencing whole chromosomes what type of methylation is needed?
You need to methylate it all
Is xist methylate in the methylated x-inactivated chromosome?
Yes
Is the xist gene methylated in the unmethylated active CpG on the active x-chromosomes?
Yes as this needs to be turned off
Xist is spread over the x-inactivated chromosomes which causes what?
DNA methylation and recruits chromatin modifications
