Developmental Genetics Programme; The Babraham Institute
In the course of normal development in mammals there are two phases of methylation reprogramming that occur. The first takes place during gametogenesis and involves the loss of DNA methylation associated to the erasure of gametic imprints thereby allowing for the essential "resetting" of these signals. The second phase of methylation reprogramming occurs after fertilization and during the brief preimplantation period where there is an asymmetric loss of methylation in the zygote. Methylation declines until the late morulae stage when de novo methylation occurs in a lineage specific manner. On cloning, the highly methylated somatic cell is introduced into an oocyte that would have ordinarily initiated some of these methylation-reprogramming events. The necessity for these events to proceed exactly in this way in order to ensure normal development is not clear. However, recent results have indicated that there is a genome wide failure to establish correct levels of methylation that may in turn lead to abnormal development and very few full term births. There is an emerging body of literature that suggests that the imposition of a DNA methylation pattern will only occur to formalize a pre-existing epigenetically established cellular memory system. The correlation that has been recognized is the relationship of DNA methylation to the modification of specific residues within the histories of the core nucleosome. The significance of these two epigenetic marking systems during early stages of mammalian development is presented. It remains to be established whether the efficiency of somatic nuclear cloning may be influenced by the fidelity of reprogramming of these parallel systems.