title: Chromosome-wide regulation of euchromatin-specific 5mC to 5hmC conversion in mouse ES cells and female human somatic cells.
abstract: DNA cytosine methylation (5mC) is indispensable for a number of cellular processes, including retrotransposon silencing, genomic imprinting, and X chromosome inactivation in mammalian development. Recent studies have focused on 5-hydroxymethylcytosine (5hmC), a new epigenetic mark or intermediate in the DNA demethylation pathway. However, 5hmC itself has no role in pluripotency maintenance in mouse embryonic stem cells (ESCs) lacking Dnmt1, 3a, and 3b. Here, we demonstrated that 5hmC accumulated on euchromatic chromosomal bands that were marked with di- and tri-methylated histone H3 at lysine 4 (H3K4me2/3) in mouse ESCs. By contrast, heterochromatin enriched with H3K9me3, including mouse chromosomal G-bands, pericentric repeats, human satellite 2 and 3, and inactive X chromosomes, was not enriched with 5hmC. Therefore, enzymes that hydroxylate the methyl group of 5mC belonging to the Tet family might be excluded from inactive chromatin, which may restrict 5mC to 5hmC conversion in euchromatin to prevent nonselective de novo DNA methylation.
authors.affiliation: Division of Molecular and Cell Genetics, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan.
authors.forename: Musashi
authors.initials: M
authors.lastname: Kubiura
authors.forename: Masaki
authors.initials: M
authors.lastname: Okano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kawamura
authors.forename: Masako
authors.initials: M
authors.lastname: Tada
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D041321:Chromosomes, Human, X / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology*; D044127:Epigenesis, Genetic; D022041:Euchromatin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005819:Genetic Markers; D018392:Genomic Imprinting; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D018626:Retroelements / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D022041:Euchromatin; D005819:Genetic Markers; D006570:Heterochromatin; D006657:Histones; D018626:Retroelements; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D001973:Bromodeoxyuridine