title: 5-Hydroxymethylcytosine: a new kid on the epigenetic block?
abstract: The discovery of the Ten-Eleven-Translocation (TET) oxygenases that catalyze the hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) has triggered an avalanche of studies aiming to resolve the role of 5hmC in gene regulation if any. Hitherto, TET1 is reported to bind to CpG-island (CGI) and bivalent promoters in mouse embryonic stem cells, whereas binding at DNAseI hypersensitive sites (HS) had escaped previous analysis. Significant enrichment/accumulation of 5hmC but not 5mC can indeed be detected at bivalent promoters and at DNaseI-HS. Surprisingly, however, 5hmC is not detected or present at very low levels at CGI promoters notwithstanding the presence of TET1. Our meta-analysis of DNA methylation profiling points to potential issues with regard to the various methodologies that are part of the toolbox used to detect 5mC and 5hmC. Discrepancies between published studies and technical limitations prevent an unambiguous assignment of 5hmC as a 'true' epigenetic mark, that is, read and interpreted by other factors and/or as a transiently accumulating intermediary product of the conversion of 5mC to unmodified cytosines.
authors.affiliation: Department of Molecular Biology, Faculties of Science and Medicine, Radboud University, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Filomena
authors.initials: F
authors.lastname: Matarese
authors.forename: Enrique
authors.initials: E
authors.lastname: Carrillo-de Santa Pau
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D044503:5-Methylcytosine / Q000502:physiology / Q000031:analogs & derivatives; D000818:Animals; D002460:Cell Line; D002843:Chromatin; D016000:Cluster Analysis; D003596:Cytosine / Q000031:analogs & derivatives* / Q000502:physiology; D019175:DNA Methylation; D053595:Embryonic Stem Cells; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010105:Oxygenases; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D002843:Chromatin; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D010105:Oxygenases