How Epigenetics Changes Gene Function

To understand the mechanisms of epigenetic regulations it is necessary to know the configuration of the genome, since this is the target of epigenetic marks. The packaging of DNA in eukaryotic cells, involves complex formation between DNA, core histones and other proteins, to form chromatin (Tollefsbol, 2009). DNA, histones and chromatin structure are related, as the DNA is wrapped around histones to form nucleosomes which then are tightly packed into chromatin, see Figure 1 (Lund 2009). Epigenetic regulation can happen on many levels such as DNA methylation, histone modifications and chromatin remodeling. (Tost 2008). The mechanism of DNA methylation is when methyl groups are added to the DNA, which normally takes place at the cytosine bases (Tost 2008). Histone modifications are changes in the properties of the histones, such as charge, shape (Lehninger, Nelson et al. 2008) and size (Allis 2007). Chromatin remodelling is a change in chromatin structure, performed by different complexes (Kundu, Dasgupta 2007).

Histone Modifications

Histones are proteins that order and pack DNA into structural units called nucleosomes. In all eukaryotic cells there are five major classes of histones, which differ in molecular weight and amino acid composition (Lehninger, Nelson et al. 2008). Typically, the nucleosome is composed of two copies of each of the four core histones; H2A, H2B, H3 and H4 with 146 basepairs of DNA wrapped around to form an octamer, see Figure (Grant 2001). The DNA is sustained around the octamer by the fifth protein family H1 (Sørensen, Falkenberg et al. 2002). Each of the core histones has a structured domain and an unstructured amino terminal of 25-40 residues, which are called the tail, and extends into the surroundings of the nucleosomes (Grant 2001). The state of the chromatin is by most part controlled by covalent modifications of histone tails. The major modifications are acetylation, phosphorylation, methylation and ubiquitylation (Tollefsbol 2009), which affect the net charge, shape or other properties of the histones (Lehninger, Nelson et al. 2008). 

Figure: Nucleosome consisting of eight core histones forming an octamer. H1 links the different nucleosomes together. Modified after (Sørensen, Falkenberg et al. 2002)

                                                                                                                           To be Continued. . . . . .