Intracellular processes Flashcards
What is epigenetics?
Changes in phenotype, without changes in genotype -> by regulation of expression
Epigenetic changes can come about as a result of influences from the environment. When is the effect of influences from the environment greatest?
If they occur early in gestation
What is lyonization?
X-inactivation in females
What are housekeeping genes?
Genes needed by (nearly) all cells
What is a nucleosome?
DNA wrapped around histones
How many types of histone are there?
4
What is the effect of DNA being wrapped around nucleosomes?
It is less accessible to transcription factors and transcription machinery
What are the two key players in regulating gene transcription?
- Transcription factors
- Gene regulatory elements
Which epigenetic mechanisms does the body have to regulate gene transcription? (4)
- DNA methylation
- Nucleosome positioning
- Histone modifications
- 3D genome folding
In which way are epigenetic modifications related to immunological memory?
After immune cells have been activated, epigenetic changes remain that allow them to quicker upregulate immunological functions -> allows for quick response
What are gene regulatory elements?
Short stretches of DNA with certain motifs, to which transcription factors can bind
In which two groups can gene regulatory elements be divided, based on proximity to the gene they regulate?
- Close to the transcription start site (=promotor)
- Distal to the transcription start site
Which gene regulatory elements can be found distal to the transcription start site? (4)
- Enhancer
- Silencer
- Insulator
- Locus control regions
What is an enhancer?
Sequence of non-coding DNA that enhances formation of transcriptional loops
What is a silencer?
A repressor of transcription activation
What is an insulator?
A gene regulatory element that prevents transcriptional looping
What is a locus control region?
A group of enhancers that work together, often in a cluster of genes
What is an example of genes which are modulated by a locus control region?
Cytokine genes
How are transcription factors (often) activated?
Signalling cascades, often from receptors
How can distal gene regulatory elements influence DNA activity if DNA is linear?
DNA is not linear, but rather folded and curled, allowing for the formation of transcriptional loops
What is the function of transcription factor Pax5? What happens when it is absent?
Needed by B-cells to differentiate and maintain B-cell phenotype
In abcence of Pax5, B-cells will differentiate into different phenotypes depending on environmental signals
True or false: after a cell has differentiated into a specific phenotype, it no longer needs its cell-type specific transcription factors
False; cells need their transcription factors to maintain their phenotype
What are mechanisms and mutations in epigenetic regulation that can lead to disease? (4)
- Mutation of regulators can block their binding to gene regulatory elements
- Fusion of regulators can lead to dysfunctional binding to enhancers
- Mutations in GRE-sequences in DNA can block (complete) binding of regulators
- Mutations in DNA sequence of GREs can weaken/strengthen binding of regulators -> phenotypic variation of gene activity
True or false: mutations in the GREs often cause complete blockage of the binding of regulators to GREs
False; often there is only partially decreased activity of regulator and not complete failure