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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10577-012-9317-9) contains supplementary material, which is available to authorized users.
Highlights
Epigenetic reprogramming activity in early embryonic cells and primordial germ cells (PGCs) induces conversion and/or replacement of DNA cytosine methylation (5mC) into unmodified cytosine (C) on a genome-wide scale (Feng et al 2010)
Tet methylcytosine dioxygenase belonging to the Tet enzyme family (Tet1-3) converts 5mC into 5-hydroxymethylcytosine (5hmC) (Tahiliani et al 2009)
We previously showed that the euchromatic marks were associated with in vitro reprogramming induced by cell fusion between embryonic stem cells (ESCs) and somatic cells (Kimura et al 2004)
Summary
Epigenetic reprogramming activity in early embryonic cells and primordial germ cells (PGCs) induces conversion and/or replacement of DNA cytosine methylation (5mC) into unmodified cytosine (C) on a genome-wide scale (Feng et al 2010). Genome-wide distribution of 5hmC was previously determined by hydroxymethylated DNA immunoprecipitation, followed by high-throughput sequencing. These studies demonstrated that 5hmC co-localises with H3K4me and H3K27me, both of which are active euchromatin marks (Ficz et al 2011; Pastor et al 2011). Tet enzymatic activity may be associated with active chromatin formation and/or maintenance in ESCs. Active chromosomal regions generally replicate in early S phase of the cell cycle, while inactive chromosomal regions, including constitutive and facultative heterochromatin, replicate in late S. G-bands are often used for identification of each chromosome ID
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
