Epigenetics
- Epigenetics involves changes in gene function, without changes to the base sequence of DNA
- All of the chemical modifications to all histone proteins and DNA (except base changes) in an organism is called the epigenome
- In eukaryotic cells, the DNA in the nucleus is wrapped around proteins called histones
- Histone proteins can be chemically modified through the addition of acetyl
- DNA can also be chemically modified through the addition of methyl groups without changing the base sequence which also leads to the regulation of gene expression
- The epigenome, like the genome, is heritable but can undergo change
- Identical twins become more distinguishable with age because despite having exactly the same DNA, their epigenomes change independently, leading to differences
- Changes to the epigenome are caused by changes in the environment
- Smoking, stress, exercise and diet can cause epigenetic changes
- Internal signalling from the body's own cells can also cause modifications to occur
- The chemical modification of histones and DNA controls how tightly the DNA is wound around them as the intermolecular bonding between the histones and DNA changes
- If the DNA is wound more tightly in a certain area, the genes on these section of DNA are 'switched off' as the gene and promoter regions are more hidden from transcription factors and RNA polymerase
- The modification of histones is reversible and therefore can be different in different cell types and can vary with age
DNA is wrapped around histone proteins which form a nucleosome. Nucleosomes coil tightly around each other to form the chromosome structure.
Acetylation of histones
- Acetyl groups (COCH3) can be added to lysine amino acids on histone proteins
- Lysine has a positively charged R group, this forms ionic bonds with the negatively charged phosphate backbone of DNA
- Adding acetyl (acetylation) to lysine residues removes the positive ion and therefore removes a bond between the histone protein and the DNA, this causes the DNA to be less tightly wrapped
- When the DNA is less tightly wrapped, RNA polymerase and transcription factors can more easily bind and therefore gene expression is stimulated
- Removal of acetyl (deacetylation) returns lysine to its positively charged state which has a stronger attraction to the DNA molecule and therefore inhibits transcription
Methylation of DNA
- Methyl groups (CH3) can be added to a carbon molecule on cytosine bases within sequences that contain multiple cytosine and guanine bases
- The addition of methyl groups (methylation) suppresses the transcription of the affected gene
- This happens because the methylated bases attract proteins that bind to the DNA and inhibit transcription