title: 5-hydroxymethylcytosine marks postmitotic neural cells in the adult and developing vertebrate central nervous system.
abstract: The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. J. Comp. Neurol. 525:478-497, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Inserm, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Université de La Réunion, UMR 1188, Sainte-Clotilde, France.|Université de La Réunion, UMR 1188, Sainte-Clotilde, France.|Inserm, UMR 1085, Research Institute in Health, Environment and Occupation, Institut National de la Santé et de la Recherche Médicale U1085, Université de Rennes 1, SFR Biosite, 9 avenue du Prof. Léon Bernard - Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Diotel
authors.affiliation: Inserm, UMR 1085, Research Institute in Health, Environment and Occupation, Institut National de la Santé et de la Recherche Médicale U1085, Université de Rennes 1, SFR Biosite, 9 avenue du Prof. Léon Bernard - Rennes, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Mérot
authors.affiliation: Inserm, UMR 1085, Research Institute in Health, Environment and Occupation, Institut National de la Santé et de la Recherche Médicale U1085, Université de Rennes 1, SFR Biosite, 9 avenue du Prof. Léon Bernard - Rennes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Coumailleau
authors.affiliation: Inserm, UMR 1085, Research Institute in Health, Environment and Occupation, Institut National de la Santé et de la Recherche Médicale U1085, Université de Rennes 1, SFR Biosite, 9 avenue du Prof. Léon Bernard - Rennes, France.
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Gueguen
authors.affiliation: UMR 6290 CNRS, IGDR, Université de Rennes 1, Campus de Beaulieu, Rennes, France.
authors.forename: Aurélien A
authors.initials: AA
authors.lastname: Sérandour
authors.affiliation: UMR 6290 CNRS, IGDR, Université de Rennes 1, Campus de Beaulieu, Rennes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salbert
authors.affiliation: Inserm, UMR 1085, Research Institute in Health, Environment and Occupation, Institut National de la Santé et de la Recherche Médicale U1085, Université de Rennes 1, SFR Biosite, 9 avenue du Prof. Léon Bernard - Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Kah
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D046169:Dermoscopy; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014981:Xenopus; D015027:Zebrafish
chemical_list: C011865:5-hydroxymethylcytosine; D049452:Green Fluorescent Proteins; D044503:5-Methylcytosine
keywords: 5hmC; 5mC; MeCP2; RRID: AB_10049650; RRID: AB_141372; RRID: AB_141607; RRID: AB_1977248; RRID: AB_2160651; RRID: AB_2572206; RRID: AB_2572207; RRID: AB_2572268; RRID: AB_477585; TET; amphibian; epigenetic; mammals; neurogenesis; teleost