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Nucleosomes help to regulate transcription in eukaryotes
Eukaryotic DNA is wrapped around histone proteins to form compact nucleosomes
- These histone proteins have protruding tails that determine how tightly the DNA is packaged
Modification of Histone Tails
Typically the histone tails have a positive charge and hence associate tightly with the negatively charged DNA
- Adding an acetyl group to the tail (acetylation) neutralises the charge, making DNA less tightly coiled and increasing transcription
- Adding a methyl group to the tail (methylation) maintains the positive charge, making DNA more coiled and reducing transcription
Types of Chromatin
When DNA is supercoiled and not accessible for transcription, it exists as condensed heterochromatin
When the DNA is loosely packed and therefore accessible to the transcription machinery, it exists as euchromatin
- Different cell types will have varying segments of DNA packaged as heterochromatin and euchromatin
- Some segments of DNA may be permanently supercoiled, while other segments may change over the life cycle of the cell
Direct methylation of DNA (as opposed to the histone tails) can also affect gene expression patterns
- Increased methylation of DNA decreases gene expression (by preventing the binding of transcription factors)
- Consequently, genes that are not transcribed tend to exhibit more DNA methylation than genes that are actively transcribed
Epigenetics
Epigenetics is the study of changes in phenotype as a result of variations in gene expression levels
- Epigenetic analysis shows that DNA methylation patterns may change over the course of a lifetime
- It is influenced by heritability but is not genetically pre-determined (identical twins may have different DNA methylation patterns)
- Different cell types in the same organism may have markedly different DNA methylation patterns
- Environmental factors (e.g. diet, pathogen exposure, etc.) may influence the level of DNA methylation within cells
Some mother rats spend a lot of time licking, grooming, and nursing their pups. Others seem to ignore their pups. Highly nurtured rat pups tend to grow up to be calm adults, while rat pups who receive little nurturing tend to grow up to be anxious.
It turns out that the difference between a calm and an anxious rat is not genetic, it's epigenetic. The nurturing behavior of a mother rat during the first week of life shapes her pups' epigenomes. And the epigenetic pattern that mom establishes tends to stay put, even after the pups become adults.
Signals from the outside world can work through the epigenome to change a cell's gene expression.
In this activity, you act as the signal. As you turn the control knob, epigenetic tags come and go to change the shape of the gene.
Notice what happens to the mRNA and protein levels when you manipulate the epigenetic tags on the gene. Gene, mRNA, and protein production are linked. They change together.
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