Epigenetics
Although all cells in multicellular organism contain essentially the same DNA, cell types and functions differ because of qualitative and quantitative differences in their gene expression. Epigenetics refers to both heritable and non-heritable changes in cell and tissue specific patterns of gene expression that are not caused by changes in DNA sequence I.e. genetic changes. The epigenetic process that stably alter gene expression patterns are thought to include:
1. Reversible modification of DNA by the addition or removal of methyl groups,
2. Posttranslational modification of histone proteins and remodelling of chromatin and
3. RNA based mechanisms.
Methylation of the 5th position of cytosine residues is a reversible covalent modification of DNA, resulting in production of 5-methylcytosine. In general, DNA methylation is associated with repression of gene expression. As DNA methylation patterns can be maintained following DNA replication and mitosis, this epigenetic modification is also associated with inheritance of the repressed state.
In addition to DNA methylation, histone modification is an important epigenetic mechanism of gene regulation. Chromatin is a dynamic structure composed of DNA wound around a histone core proteins to form nucleosomes. The N-terminal region of each histone extends beyond the nucleosome, and the Ami no acids in these tails can be covalently modified in several ways, including the addition of acetyl, methyl and phosphate groups. Several sets of proteins are involved in modifying histones. These include proteins that add chemical groups to histones. Proteins that interpret those modifications, and proteins that remove those chemical groups. These modifications alter the structure of chromatin, making genes on nucleosomes available or inaccessible for transcription. Hostone acetylation, for example, makes genes on these modified nucleosomes available for transcription. This modification is reversible and removing acetyl groups changes the chromatin confirmation from an open to closed configuration, silencing genes by making them unavailable for transcription. The specific combinations of histone modifications control the transcription status of chromatin region. Many combinations of histone modifications are possible, and the sum of the complex patterns and interactions of histone modifications that alter chromatin organization and gene expression is called the histone code. Combinations of these changes allow differentiated cells to carry out cell specific patterns of gene transcription and to respond to external signals that modify these patterns without any changes in DNA sequence.
RNA based mechanisms of epigenetic regulation are less well understood than mechanisms based on DNA methylation and histones. A number of non-coding RNAs play important roles in modifying the sequence, structure, or expression of mRNAs and therapy also changes the protein expression from these genes.