Why is DNA methylation of Igf2 CpG island shore affected during ageing?
ABSTRACT Comment on: Pirazzini C, Giuliani C, Bacalini MG, Boattini A, Capri M, Fontanesi E, Marasco E, Mantovani V, Pierini M, Pini E, Luiselli D, Franceschi C. Garagnani P. Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age. AGING: V4, N7.
Full-textDOI: · Available from: Michele Zampieri, Oct 01, 2014
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ABSTRACT: Induced pluripotent stem (iPS) cells are derived by epigenetic reprogramming, but their DNA methylation patterns have not yet been analyzed on a genome-wide scale. Here, we find substantial hypermethylation and hypomethylation of cytosine-phosphate-guanine (CpG) island shores in nine human iPS cell lines as compared to their parental fibroblasts. The differentially methylated regions (DMRs) in the reprogrammed cells (denoted R-DMRs) were significantly enriched in tissue-specific (T-DMRs; 2.6-fold, P < 10(-4)) and cancer-specific DMRs (C-DMRs; 3.6-fold, P < 10(-4)). Notably, even though the iPS cells are derived from fibroblasts, their R-DMRs can distinguish between normal brain, liver and spleen cells and between colon cancer and normal colon cells. Thus, many DMRs are broadly involved in tissue differentiation, epigenetic reprogramming and cancer. We observed colocalization of hypomethylated R-DMRs with hypermethylated C-DMRs and bivalent chromatin marks, and colocalization of hypermethylated R-DMRs with hypomethylated C-DMRs and the absence of bivalent marks, suggesting two mechanisms for epigenetic reprogramming in iPS cells and cancer.Nature Genetics 11/2009; 41(12):1350-3. DOI:10.1038/ng.471 · 29.65 Impact Factor
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ABSTRACT: In mammalian cells, the replication of genetic and epigenetic information is directly coupled; however, little is known about the maintenance of epigenetic information in DNA repair. Using a laser microirradiation system to introduce DNA lesions at defined subnuclear sites, we tested whether the major DNA methyltransferase (Dnmt1) or one of the two de novo methyltransferases (Dnmt3a, Dnmt3b) are recruited to sites of DNA repair in vivo. Time lapse microscopy of microirradiated mammalian cells expressing GFP-tagged Dnmt1, Dnmt3a, or Dnmt3b1 together with red fluorescent protein-tagged proliferating cell nuclear antigen (PCNA) revealed that Dnmt1 and PCNA accumulate at DNA damage sites as early as 1 min after irradiation in S and non-S phase cells, whereas recruitment of Dnmt3a and Dnmt3b was not observed. Deletion analysis showed that Dnmt1 recruitment was mediated by the PCNA-binding domain. These data point to a direct role of Dnmt1 in the restoration of epigenetic information during DNA repair.Proceedings of the National Academy of Sciences 07/2005; 102(25):8905-9. DOI:10.1073/pnas.0501034102 · 9.81 Impact Factor
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ABSTRACT: The role of epigenetics in aging and age-related diseases is a key issue in molecular physiology and medicine because certain epigenetic factors are thought to mediate, at least in part, the relationship between the genome and the environment. An active role for epigenetics in aging must meet two prior conditions: there must be specific epigenetic changes during aging and they must be functionally associated with the aged phenotype. Assuming that specific epigenetic modifications can have a direct functional outcome in aging, it is also essential to establish whether they depend on genetic, environmental or stochastic factors, and if they can be transmitted from one generation to the next. Here we discuss current knowledge about these matters and future directions in the field.Ageing research reviews 11/2009; 8(4):268-76. DOI:10.1016/j.arr.2009.03.004 · 7.63 Impact Factor