title: DNA demethylation, Tet proteins and 5-hydroxymethylcytosine in epigenetic reprogramming: an emerging complex story.
abstract: Epigenetic reprogramming involves processes that lead to the erasure of epigenetic information, reverting the chromatin template to a less differentiated state. Extensive epigenetic reprogramming occurs both naturally during mammalian development in the early embryo and the developing germ line, and artificially in various in vitro reprogramming systems. Global DNA demethylation appears to be a shared attribute of reprogramming events, and understanding DNA methylation dynamics is thus of considerable interest. Recently, the Tet enzymes, which catalyse the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine, have emerged as potential drivers of epigenetic reprogramming. Although some of the recent studies point towards the direct role of Tet proteins in the removal of DNA methylation, the accumulating evidence suggests that the processes underlying DNA methylation dynamics might be more complex. Here, we review the current evidence, highlighting the agreements and the discrepancies between the suggested models and the experimental evidence.
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Faculty of Medicine, Du Cane Road, W12 0NN London, UK.
authors.forename: Peter W S
authors.initials: PW
authors.lastname: Hill
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Faculty of Medicine, Du Cane Road, W12 0NN London, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Amouroux
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Faculty of Medicine, Du Cane Road, W12 0NN London, UK. Electronic address: petra.hajkova@csc.mrc.ac.uk.
authors.forename: Petra
authors.initials: P
authors.lastname: Hajkova
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism* / Q000031:analogs & derivatives; D000818:Animals; D065150:Cellular Reprogramming; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction
chemical_list: D004268:DNA-Binding Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5-Hydroxymethylcytosine; Demethylation; Germ cells; Methylation; Reprogramming; Tet; iPS