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Concept
Reprogramming
Summary
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
Reprogrammings that are both large scale (10% to 100% of epigenetic marks) and rapid (hours to a few days) occur at three life stages of mammals. Almost 100% of epigenetic marks are reprogrammed in two short periods early in development after fertilization of an ovum by a sperm. In addition, almost 10% of DNA methylations in neurons of the hippocampus can be rapidly altered during formation of a strong fear memory.
After fertilization in mammals, DNA methylation patterns are largely erased and then re-established during early embryonic development. Almost all of the methylations from the parents are erased, first during early embryogenesis, and again in gametogenesis, with demethylation and remethylation occurring each time. Demethylation during early embryogenesis occurs in the preimplantation period. After a sperm fertilizes an ovum to form a zygote, rapid DNA demethylation of the paternal DNA and slower demethylation of the maternal DNA occurs until formation of a morula, which has almost no methylation. After the blastocyst is formed, methylation can begin, and with formation of the epiblast a wave of methylation then takes place until the implantation stage of the embryo. Another period of rapid and almost complete demethylation occurs during gametogenesis within the primordial germ cells (PGCs). Other than the PGCs, in the post-implantation stage, methylation patterns in somatic cells are stage- and tissue-specific with changes that presumably define each individual cell type and last stably over a long time.
The mouse sperm genome is 80–90% methylated at its CpG sites in DNA, amounting to about 20 million methylated sites. After fertilization, the paternal chromosome is almost completely demethylated in six hours by an active process, before DNA replication (blue line in Figure).
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