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Epigenetics
Epigenetics is the study of changes in phenotype as a result of variations in gene expression levelsÂ
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
Epigenetic Control: Regulating Access to Genes within the Chromosome
Epigenetic Control: Regulating Access to Genes within the Chromosome
One reason why eukaryotic gene expression is more complex than prokaryotic gene expression is because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with control of access to the DNA. This form of regulation, called epigenetic regulation, occurs even before transcription is initiated.
One reason why eukaryotic gene expression is more complex than prokaryotic gene expression is because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at many different levels. Eukaryotic gene expression begins with control of access to the DNA. This form of regulation, called epigenetic regulation, occurs even before transcription is initiated.
The human genome encodes over 20,000 genes; each of the 23 pairs of human chromosomes encodes thousands of genes. The DNA in the nucleus is precisely wound, folded, and compacted into chromosomes so that it will fit into the nucleus. It is also organized so that specific segments can be accessed as needed by a specific cell type.
The first level of organization, or packing, is the winding of DNA strands around histone proteins. Histones package and order DNA into structural units called nucleosome complexes, which can control the access of proteins to the DNA regions. Under the electron microscope, this winding of DNA around histone proteins to form nucleosomes looks like small beads on a string. These beads (histone proteins) can move along the string (DNA) and change the structure of the molecule.
Epigenetic Gene Regulation
Epigenetic Gene Regulation
Eukaryotic gene expression regulation is more complex than in prokaryotes. Because eukaryotes have large linear chromosomes that are compacted within cells, accessing the genes that are wrapped around histones is another way in which expression can be regulated. This is epigenetics.
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) neutralizes 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
If DNA encoding a specific gene is to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down the DNA to open that specific chromosomal region and allow for the transcriptional machinery (RNA polymerase) to initiate transcription Nucleosomes can move to open the chromosome structure to expose a segment of DNA, but do so in a very controlled manner.
A. Histone Acetylation
A. Histone Acetylation
Histone acetylation is a critical epigenetic modification that changes chromatin architecture and regulates gene expression by opening or closing the chromatin structure. It plays an essential role in cell cycle progression and differentiation.
B. Methylation
Epigenetic modification to the DNA itself also occurs.
The most common modification is the addition of a methyl group to cytosine nucleotides.
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription
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
Agouti Gene in MICE
Experiments in mice show just how important a mother's diet is in shaping the epigenome of her offspring. All mammals have a gene called agouti. When a mouse's agouti gene is completely unmethylated, its coat is yellow and it is obese and prone to diabetes and cancer. When the agouti gene is methylated (as it is in normal mice), the coat color is brown and the mouse has a low disease risk. Fat yellow mice and skinny brown mice are genetically identical. The fat yellow mice are different because they have an epigenetic "mutation."
When researchers fed pregnant yellow mice a methyl-rich diet, most of her pups were brown and stayed healthy for life. These results show that the environment in the womb influences adult health. In other words, our health is not only determined by what we eat, but also by what our parents ate.
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