What is epigenetics? [3]
- The effect of environmental influences altering the expression of genes
- These alterations may be inherited by subsequent generations
- These inheritable changes in gene function occur without altering the base sequence of DNA
What could epigenetics potentially cure?
Epigenetic research could lead us to cures for:
cancer, gestational diabetes & other diseases/disorders
The Epigenome [4]
- DNA and histones can be covered in chemical ‘tags’ - acetyl and methyl groups
- Tags are the epigenome
- Tags determine the shape of the histone-DNA complex (how tightly or loosely bound sections are)
- Environmental changes alter chemical tags (methyl & acetyl) associated with DNA, affecting gene expression
Inactive Genes
Inactive genes can be wrapped tightly and become inaccessible, meaning they are not transcribed
(epigenetic silencing)
Active Genes
Active genes are ‘looser’ and are more easily transcribed, meaning transcription factors can access promoter regions
Transcription can be inhibited by:
- Increased methylation of the DNA
- Decreased acetylation of associated histones
Methylation
Methylation = addition of methyl group to cytosine bases which reduces gene expression
Increased methylation (hypermethylation) = decreased transcription
Methylation can: [2]
- Prevent binding of transcription factors
- Attract proteins that condense the DNA-histone complex (by inducing deacetylation of the histones) so that they become inaccessible to transcription factors
Acetylation
Acetylation of histones = increased transcription
Process of Acetylation [2]
- Acetyl groups added to histones opens the DNA coiling, allowing transcription.
- Decreased acetylation of histones inhibits transcription, as transcription factors can’t access the DNA
The DNA-histone complex
A weak association with histone:
- loosely packed DNA
- DNA is accessible by transcription factors
- mRNA can be made
Strong association with histone:
- tightly packed
- not accessible by transcription factors
- no mRNA made
Methylation Summary
Methylation is on cytosine bases.
Methylation makes the DNA structure tighter.
Increased methylation = decreased transcription
Decreased methylation = increased transcription
Acetylation Summary
Acetylation is on histone proteins.
Acetylation makes the DNA structure looser.
Increased acetylation = increased transcription
Decreased acetylation = decreased transcription
Give an example of Epigenetics
Dutch Hunger Winter (Nov 1944 - April 1945)
Mothers who experienced malnourishment in their first trimester of pregnancy often gave birth to babies of normal weight despite lack of food, whereas those in the third trimester would often give birth to underweight babies.
Epigenetic tagging allowed the foetus to put more rapid weight increase on compared to normal.
This tagging was inherited by the next generation, which caused them to be a greater birthweight (obese) compared to normal.
Other examples:
- Well treated rats respond better to stress and nurture their young
- Strong evidence there is epigenetic influence in gestational diabetes, passing between generations
Epigenetics and Disease [2]
- Epigenetic modifications have been linked to different diseases, by overexpressing genes or by silencing other
- Certain cancers have been linked to this, some due to having less methylation (more expression), others to more methylation (less expression)
Diseases induced by this can be treated by: [2]
- Drugs to inhibit enzymes involved in acetylation or methylation
- Inhibit enzymes that cause methylation = reactivating silenced genes (MUST be specific to the cancer genes though could cause cancer elsewhere because of activated genes)
Diagnosing Disease
- Identify methylation and acetylation of certain genes relative to ‘normal’ levels
- Could test for: cancer, brain disorders and arthritis
Early detection = early treatment = higher survival rate
