Understanding the principle of epigenetics has allowed for the creation of drugs that switch
on or off epigenetic mechanisms
Phenotype is determined by genotype and environment (controlled in part by epigenetic
mechanisms)
Explains how multiple phenotypes can be generated from the same genotype
o Housekeeping genes code for proteins that are found in all cells- histones, RNA
polymerase, tubulin. Not greatly affected by epigenome
o Specialised genes determined specific features of different cells i.e. acetyl choline
esterase in neurons, troponin in skeletal muscle
The process of differentiation is simply a pathway were different genes are tuned on and off.
NO DNA IS LOST
As the range of protein expression increases, abundance decreases
Epigenetics depends on mechanisms that regulate gene expression, where the predominant
level of control is found in regulating transcription
Quantity of RNA to equivalent to amount of protein produced
Gene= transcriptional units composed of structural information coding for a protein and regulatory
sequences giving instructions for expression i.e. the promoter region
Promoter region
5' regulatory sequence controls transcription initiation
Many promoters contain a TATA box (thymine, adenine, thymine, adenine) approximately
25 base pairs from the start of a gene
To initiate transcription TFIID binds to the TATA box, followed by additional basal machinery
that build up to form the holoenzyme RNA polymerase (large complex of proteins). This also
produces a kink in the DNA, and together they begin transcription
However, experiments were only basal factors showed that transcription is very inefficient . Instead
gene specific transcription factors are added to activate transcription and reach maximum level.
Regulatory proteins and enhancer DNA segments are found close to and far away from the gene
being transcribed. These control the rate of transcription.
NOTE- Remember that DNA coils very tightly (spaghetti like) and so enhancers that are far away
linearly may be close to gene when folded correctly
Transcription activators bind to enhancer regions of DNA and tell the RNA polymerase "when to
fire", as well as controlling the transcription rate. These activators can interact with environmental
factors such as phosphate levels, extracellular steroids, heat-shock etc and alter the rate of
transcription, even inhibiting it entirely. Thus, the quantity of a specific protein produced by the cell
may change, impacting the phenotype of the cell.
DNA Organisation
Only exists as visible chromosomes when cells divide via mitosis