A8. Epigenetic Control of Gene Expression Flashcards
How does epigenetic control work?
What do they control in eukaryotes?
How does it work?
What do they not do?
What do they do instead?
What do epigenetic changes do to gene expression?
How can epigenetic changes occur and how?
- In eukaryotes, epigenetic control can determine whether a gene is switched on or off i.e. whether the gene is expressed (transcribed and translated) or not.
- It works through the attachment or removal of chemical groups (known as epigenetic marks) to or from DNA or histone proteins.
- These epigenetic marks don’t alter the base sequence of DNA
- Instead, they alter how easy it is for the enzymes and other proteins needed for transcription to interact with and transcribe the DNA.
Epigenetic changes to gene expression play a role in lots of normal cellular processes and can also occur in response to changes in the environment-e.g. pollution and availability of food.
Inheriting epigenetic changes (3 things)
Example - plants?
- Organisms inherit their DNA base sequence from their parents.
- Most epigenetic marks on the DNA are removed between generations, but some escape the removal process and are passed on to offspring.
- This means that the expression of some genes in the offspring can be affected by environmental changes that affected their parents or grandparents.
Example
Epigenetic changes in some plants in response to drought have been shown to be passed on to later generations
Controlling gene expression - Increased methylation of DNA
What is methylation?
Where does it attach and what is that?
What does increased methylation do and what is its effect?
- Methylation is when a methyl group (an example of an epigenetic mark) is attached to the DNA coding for a gene.
- The group always attaches at a CpG site, which is where a cytosine and guanine base are next to each other in the DNA (linked by a phosphodiester bond).
- Increased methylation changes the DNA structure so that the transcriptional machinery (enzymes, etc.) can’t interact with the gene-so the gene is not expressed (i.e. it’s switched off).
Figure 1: DNA strand with a methyl group attached.
Controlling gene expression - Decreased acetylation of histones
What are histones?
What is variable about chromatin and what is its effect?
How can histones be epigenetically modified?
What does this mean?
What enzymes are involved and what do they do?
- Histones are proteins that DNA wraps around to form chromatin, which makes up chromosomes.
- Chromatin can be highly condensed or less condensed. How condensed it is affects the accessibility of the DNA and whether or not it can be transcribed.
- Histones can be epigenetically modified by the addition or removal of acetyl groups (which are another example of an epigenetic mark). When histones are acetylated, the chromatin is less condensed.
This means that:
- the transcriptional machinery can access the DNA, allowing genes to be transcribed. - When acetyl groups are removed from the histones, the chromatin becomes highly condensed and genes in the DNA can't be transcribed because the transcriptional machinery can't physically access them.
Histone deacetylase (HDAC) enzymes are responsible for removing the acetyl groups
Figure 2: Highly condensed chromatin (left) and less condensed chromatin (right).
Treating disease
Epigenetic changes are ___________, which makes them good targets for new drugs to combat diseases they cause. These drugs are _________ to counteract the epigenetic changes that cause the diseases.
For example, __________ _____________is an epigenetic change that can lead to a gene being switched off. Drugs that stop DNA ____________can sometimes be used to treat diseases caused in this way
Decreased ______________of _________can also lead to genes being switched ___. HDAC inhibitor drugs, e.g. romidepsin, can be used to treat diseases that are caused in this way - including some types of cancer. These drugs work by inhibiting the activity of histone deacetylase (HDAC) __________, which are responsible for removing the acetyl groups from the histones. Without the activity of HDAC enzymes, the genes remain acetylated and the proteins they code for can be ____________.
The problem with developing drugs to counteract epigenetic changes is that these changes take place normally in a lot of cells, so it’s important to make sure the drugs are as _________ as possible. Eg. drugs used in cancer therapies can be designed to only target dividing cells to avoid damaging normal body cells.
Treating disease
Epigenetic changes are reversible, which makes them good targets for new drugs to combat diseases they cause. These drugs are designed to counteract the epigenetic changes that cause the diseases.
For example, increased methylation is an epigenetic change that can lead to a gene being switched off. Drugs that stop DNA methylation can sometimes be used to treat diseases caused in this way
Decreased acetylation of histones can also lead to genes being switched off. HDAC inhibitor drugs, e.g. romidepsin, can be used to treat diseases that are caused in this way - including some types of cancer. These drugs work by inhibiting the activity of histone deacetylase (HDAC) enzymes, which are responsible for removing the acetyl groups from the histones. Without the activity of HDAC enzymes, the genes remain acetylated and the proteins they code for can be transcribed.
The problem with developing drugs to counteract epigenetic changes is that these changes take place normally in a lot of cells, so it’s important to make sure the drugs are as specific as possible. Eg. drugs used in cancer therapies can be designed to only target dividing cells to avoid damaging normal body cells.
Tip: If these drugs that counteract epigenetic changes also activate _____________in normal cells, the cells could become cancerous, creating the very problem that the drugs are supposed to be treating.
Tip: If these drugs that counteract epigenetic changes also activate transcription in normal cells, the cells could become cancerous, creating the very problem that the drugs are supposed to be treating.
