Epigenetic Control Of Gene Expression Flashcards
(23 cards)
What is meant by epigenetics
It’s the process by which environmental factors can cause heritable changes in gene function without changing the base sequence of DNA
What is the epigenome
Chemical tags on DNA and histones form a second layer known as epigenome
What does the epigenome determine
The shape of the DNA histone complex
E.g. keeps genes that are inactive in a tightly packed arrangement and therefore ensures that they cannot be read (keeps them switched off) - this is known as epigenetic silencing
or
It unwraps active genes so that the dna is exposed and can easily be transcribed (switches them on)
What is epigenetic silencing
keeps genes that are inactive In a tightly packed arrangement and therefore ensures that they cannot be read (keeps them switched off)
Why is the epigenome flexible
Because it’s chemical tags respond to environmental changes.
Factors like diet and stress can cause the chemical tags to adjust the wrapping and unwrapping of dna and so switch genes on and off
What is important in shaping the epigenome in early development
The signals come from within the cells of the fetus and the nutrition provided by the mother
The environmental signal stimulates proteins to carry its message inside the cell from where it is passed 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 in the dna. Once attached the protein has two possible effects, what can it change ?
Acetylation of histones leading to the activation or inhibition a gene
Methylation of DNA by attracting enzymes that can add or remove methyl groups
Where the association of histones with DNA is weak, what’s the dna-histone complex like
It is less condensed (loosely packed)
What can the dna histone complex do when it’s less condensed
It is accessible by transcription factors, which can initiate production of mRNA, that is, can switch the gene on
What’s the condition like when the association is stronger between the dna histone complex
It’s more condensed, the DNA is not accessible by transcription factors, which therefore cannot initiate production of mRNA, that is, the gene is switched off
What does condensation of the DNA histone complex do?
Inhibits transcription
It can be brought about by decrease acetylation of these histones or by methylation of DNA
What is acetylation
An acetyl group is transferred to a molecule
What’s deacetylation
Is the reverse reaction where an acetyl group is removed from a molecule
What does a decreased acetylation do
Increase the positive charges on histones and therefore increases their attraction to the phosphate groups of DNA
The association between dna and histones is stronger and the dna is not accessible to transcription factors.
These transcription factors cannot initiate mRNA production from DNA. In other words, the gene is switched off
What is methylation
Is the addition of a methyl group (CH3) to a molecule
How does methylation inhibit transcription of genes in 2 ways?
Preventing the binding of transcriptional factors to the DNA
Affecting proteins that condense the DNA- histone complex (by inducing deacetylation of the histones) making the DNA inaccessible to transcription factors
What’s the effect on DNA DNA-histone complex Chromatin type Transcription factors Gene
If there is a decreased acetylation in the histones
DNA- increased methylation DNA-histone complex - more condensed Chromatin type-heterochromatin Transcription factors-no access Gene - inactive
What’s the effect on DNA DNA-histone complex Chromatin type Transcription factors Gene
If there is a increased acetylation in the histones
DNA- decreased methylation DNA-histone complex- less condensed Chromatin type- euchromatin Transcription factors- access Gene - active
What can altering the epigenetic processes do
Can cause abnormal activation or silencing of genes
What can increased methylation do to lead to cancer
Has led to protective genes been switched off. As a result, damaged base sequences in DNA are not repaired and can lead to cancer
How can we treat diseases with epigenetic therapy
drugs that inhibit enzymes that cause DNA methylation can reactivate genes that have been silenced.
Can do tests that can identify the level of DNA methylation and histone acetylation at an early stage of disease - allowing a better chance to seek early treatment
Describe the mechanism involving small double stranded sections of siRNA
- An enzyme cuts large double stranded molecules of RNA into smaller sections called small interfering RNA (siRNA)
- One of the two siRNA strands combines with an enzyme
- The siRNA molecule guides the enzyme to a mRNA molecule by pairing up its bases with the complimentary ones on a section of the mRNA molecule
- The mRNA is no longer capable of being translated into a polypeptide
- This means that the gene has not been expressed, that is, it has been blocked
One of the 2 strands of siRNA combines with an enzyme and guides it to an mRNA molecule which it then cuts. Explain why the mRNA is unlikely to be cut if the other siRNA strand combines with the enzyme
The other strand would have complimentary bases. It is unlikely that these opposite base pairings would complement a sequence of the mRNA. The siRNA, with enzyme attached, would therefore not bind to the mRNA and so would be unaffected