tailieunhanh - Báo cáo y học: "Genome-wide DNA demethylation in mammals"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Genome-wide DNA demethylation in mammals. | Sanz et al. Genome Biology 2010 11 110 http 2010 11 3 110 w Genome Biology RESEARCH HIGHLIGHT L__ Genome-wide DNA demethylation in mammals Lionel A Sanz Satya K Kota and Robert Fell Abstract The cytidine deaminase AID and elongator-complex proteins contribute to the extensive removal of DNA methylation in mammalian primordial germ cells and in the paternal pronucleus of the zygote. In mammalian genomes DNA methylation is found at cytosine residues that are followed by guanines. This epigenetic modification is essential for the repression of retrotransposons and other elements of foreign origin it regulates developmental genes including the pluripotency genes OCT4 and NANOG and is crucial for genomic imprinting. CpG methylation undergoes dramatic global changes at specific stages of mammalian development. These include acquisition of new methylation patterns early in development genome-wide removal of DNA methylation in the primordial germ cells PGCs and following fertilization removal of DNA methylation from the sperm-derived genome 1 and references therein . Whereas the acquisition of DNA methylation is now well understood the mechanisms involved in global DNA demethylation in PGCs and the zygote had remained elusive. Two exciting recent studies 2 3 now show that the cytidine deaminase AID contributes to active DNA demethylation in mammals. Another remarkable study has discovered that components of the elongator complex are involved in the process as well 4 . After fertilization the sperm-derived pronucleus undergoes a rapid global loss of DNA methylation which occurs independently of DNA replication. Some genes however including imprinted genes show resistance to this active demethylation process. The maternal pronucleus is also resistant but undergoes passive replicationdependent demethylation during the first few cell cycles of development. Consequently by the blastocyst stage both the parental genomes have acquired low .