title: 5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels.
abstract: We recently identified a class of neuronal gene inheriting high levels of intragenic methylation from the mother and maintaining this through later development. We show here that these genes are implicated in basic neuronal functions such as post-synaptic signalling, rather than neuronal development and inherit high levels of 5mC, but not 5hmC, from the mother. 5mC is distributed across the gene body and appears to facilitate transcription, as transcription is reduced in DNA methyltransferase I (Dnmt1) knockout embryonic stem cells as well as in fibroblasts treated with a methyltransferase inhibitor. However in adult brain, transcription is more closely associated with a gain in 5hmC, which occurs without a measurable loss of 5mC. These findings add to growing evidence that there may be a role for 5mC in promoting transcription as well as its classical role in gene silencing.
authors.affiliation: Centre for Molecular Biosciences, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Rachelle E
authors.initials: RE
authors.lastname: Irwin
authors.affiliation: Centre for Molecular Biosciences, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Avinash
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Centre for Molecular Biosciences, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Karla M
authors.initials: KM
authors.lastname: O' Neill
authors.affiliation: Centre for Molecular Biosciences, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK. Electronic address: cp.walsh@ulster.ac.uk.
authors.forename: Colum P
authors.initials: CP
authors.lastname: Walsh
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism* / Q000031:analogs & derivatives; D000818:Animals; D001921:Brain / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018392:Genomic Imprinting; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; 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
keywords: 5′-Hydroxymethylation; 5′-Methylcytosine; Development; Epigenetics; Gametes; Neuronal function