Epigenetic markers

CenH3 is selectively and quantitatively retained in the mature spermatozoa and it forms discrete foci in the nucleus (Palmer et al, 1990). This suggests that information on the centromeric organization of chromatin is transmitted through generations and thus, CenH3 could act as a specific epigenetic marker. 

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]. 

Figure 11.3. Two complementary strands of DNA are held together by base pairing where G C pairs make three hydrogen bonds and A-T pairs have two H bonds. For C, the H indicated in bold can be replaced by a CH3 group yielding 5-MeC, an epigenetic marker. In RNA, the CH3 group of T is replaced by an H (making U) and all the 2 positions (bold-faced H on sugars) carry OH groups instead of H.

Finally, a third approach has been proposed with five stages that focus on the chemical structure, DNA-reactivity, epigenetic effects, limited bioassays, and finally, the application of accelerated bioassays. These accelerated bio assays require 40 weeks and apply to the use of sensitive markers for induction of neoplasia in comparison to positive control compounds for important organs in human carcinogenesis. It enables data acquisition of the entire carcinogenesis process directed toward developing mechanistic information. This system would have the potential to replace the chronic bioassay in rodents in some circumstances and could serve a analternative to a chronic bioassay in a second species. ... 

Schmidt U, Holsboer F, Rein T (2011) Epigenetic aspects of posttraumatic stress disorder. Dis Markers 30(2-3) 77-87... 

In contrast to the in vivo genetic markers whose modes of inheritance are known at the organism level, a variant isolated in mammalian cell cultures may not necessarily represent a true genetic alteration. Therefore, the important task, after isolation from a selection experiment, is to determine the genetic or epigenetic nature of such variants. 

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