20.4 Epigenetic control of gene expression Flashcards
What is epigenetics
Provides explanations for why our environment eg diet, stress, toxins can change the genetic inheritance of an organisms offspring
What is the epigenome
How does it affect the transcription of genes
DNA is wrapped around histone proteins, and these are both covered in chemicals called tags.
These chemical tags form a second layer called epigenome which determines shape of DNA histone complex.
It keeps genes that are inactive in a tight arrangement so ensures they can’t be read (to keep them switched off).
It also unwraps active genes to expose the DNA so it can be transcribed
DNA is fixed but epigenome is flexible.
Why
The epigenomes chemical tags respond to environmental changes. Factors like diet and stress can cause the chemical tags to adjust the wrapping and unwrapping of DNA so switch genes on and off.
How does the epigenome of a cell act like a cellular memory
- It accumulates signals it has received in its lifetime
- Eg signals from within cells of the fetus and nutrition provided from its mother
- These factors are important in shaping the epigenome at this stage
- Then after birth, environmental factors affect epigenome and also hormones in the body.
They can cause epigenome to activate or inhibit certain genes
The environmental signal stimulates proteins to carry its message to the DNA
How
Proteins inside the cell carry its message by a series of other proteins into the nucleus.
Here the message passes to a specific protein which can be attached to a specific sequence of bases on the DNA
Once an environmental signal is attached to protein, what are the two possible affects
- It can change acetylation of histones leading to activation or inhibition of a gene
- It can change methylation of DNA by attracting enzymes that can add or remove methyl groups
The DNA- histone complex has parts that are strong and weak, how
- Where the association of histones with DNA is weak, the complex is less condensed so is loosely packed
Where the association is stronger, the DNA histone complex is more condensed and tightly coiled
In parts of complex that are weak, how can this switch a gene on
If DNA and histone are weak the complex is more open
This means the DNA is accessible by transcription factors which can stimulate production of mRNA and switch the gene on
In parts of complex that are strong, how can this switch a gene off
DNA histone complex is more condensed so is not accessible by transcription factors
These can’t initiate production of mRNA so gene is switched off
What two methods can cause condensation of DNA histone complex to stop mRNA production
Decreased acetylation of associated histones
Increased methylation of DNA
What is acetylation
What is deacetylation
Process where acetyl group is transferred to a molecule. Acetyl group is CH3CO-R
It is donated by acetylcoenzyme A from link reaction in respiration
Deacetylation is removing acetyl from molecule
How does decreased acetylation of associated histones inhibit transcription
This means less acetyl groups are being added to histone
This increases the positive charge on histones so increases their attraction to negative phosphate groups on DNA.
The association between histones and DNA is stronger so condense to stop DNA being accessible to transcriptional factors, so gene is switched off
How does increased methylation of DNA inhibit transcription
Methylation is the addition of a methyl group CH3 to a molecule. So it is added to cytosine bases of DNA
- This prevents binding of transcriptional factors to DNA
- This attracts proteins that condense the DNA histone complex (by inducing deacetylation of the histones) which makes DNA inaccessible to transcriptional factors
Why is it probable that epigenetic inheritance doesn’t take place
- Experiment on rats shows that female offspring that receieve good care when young respond better to stress later on in life and themselves nurture their offspring.
- Female offspring who received low quality care at birth nurture their offspring less well.
Good maternal behavior in rats transmits epigenetic information onto their offsprings DNA without passing through egg or sperm
What is genetic clean state
In sperm and egg cells during earliest stage of development, a specialised cellular mechanism searches the genome and erases its epigenetic tags
This leaves the cells at a clean state however some tags can escape this process and pass from parent to offspring unchanged
How can epigenetic changes cause disease
Epigenetic processes can be altered and can cause abnormal activation or silencing of genes.
Activation of a normally inactive gene can cause cancer, or inactivation of a normally active gene causes cancer
Scientists found that patients with cancer had less DNA methylation than DNA of normal people
How does this support theory
Less DNA methylation means transcription is not inhibited so the genes are still switched on.
So patients with less DNA methylation have higher than normal gene activity
How do we treat disease with epigenetic therapy
Use drugs to inhibit certain enzymes involved in histone acetylation or DNA methylation
Drugs that inhibit enzymes causing DNA methylation can reactivate genes that have been silenced.
However this can only be used on cancer cells, not normal cells as this could cause gene transcription and make them cancerous
Epigenetics can also be in diagnostics to test for early stages or cancer, arthritis etc. The tests can find level of DNA methylation and histone acetylation at start of disease.
What is RNA interference
This is inhibiting translation of mRNA by breaking it down before its coded information is transcribed
What is the process of RNA interference
- An enzyme cuts large double stranded molecules of RNA into smaller sections called siRNA (small interfering RNA)
- One of the two siRNA strands combines with the enzyme and guides it to an mRNA molecule then pairs their complimentary bases
- The enzyme can then cut mRNA into smaller sections so mRNA is no longer capable of being translated into a polypeptide.
So gene has been blocked.
