Brief introduction to DNA methylation

The methylation of DNA at CpG islands has also turned out to be an important regulator for cell development, the differentiated proteome and the regulation of cell survival [237,238]. Indeed the implications of this chemical modification have been linked to DNA accessibility, chromatin fluidity and cell transformation [239,240]. DNA methylation is required for genomic stability and believed to act as an inert epigenetic marker in germinal cells and preimplantation embryos [238]. Presumably, DNA methylation is required for the heritable transmission of chromatin structure, which prevents the expression of terminally silenced genes in differentiated tissues, and provides a host-defense mechanism against parasitic transposable elements [241]. 

Although chemically modifying DNA have distinctive implications for chromatin transitions and fiber structure in the presence of HI [250], in vivo these effects appear to work in concert with chromosomal proteins. 5 -Methylcytosines are specifically bound by members of the MBD (methyl-CpG-binding-domain) family, such as MeCP2 (Methyl-Cytosine binding Protein 2) and MBDl. These proteins have been shown to interact with HDACs and provide a casual link between DNA methylation, histone deacetylation and transcriptional repression [251-253]. 

Recently, a connection between histone methylation and DNA methylation has been made in Neuospora crassa [254,255]. This discovery outlines a redundant relationship between two distinct mechanisms for the selective repression of DNA and formation of heterochromatin, as both of these effects have been shown to facilitate the formation of restrictive chromatin architectures [256]. Importantly, this significant observation has implications for proviral repression [257], and physiologic development and disease prevention [258]. 

A significant portion of the histone variability described in the previous sections affects the electrostatic charge or hydrophobic character of these proteins particularly at the N- and C-terminal regions of the molecule. While some of these modifications appear to be used as a coding mechanism [121,123,165] (see histone code hypothesis, Fig. 5), the changes in the polarity also most likely play an additionally important role in the modulation of the histone-DNA 

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