Ential importance of this modification in the human brain. A searchable database of our fetal brain 5hmC data is available as a resource to the research community at http://www. epigenomicslab.com/online-data-resources.Background Human brain development is characterized by coordinated changes in gene expression mediated by a complex interaction between transcription factors [1] and epigenetic processes [2]. We recently characterized the dramatic alterations in DNA methylation (5-methylcytosine, 5mC) occurring during human neurodevelopment [3], but little is known about the role of other epigenetic modifications during this period. Of particular interest is DNA hydroxymethylation (5-hydroxymethylcytosine, 5hmC), a covalent modification of cytosine that represents an oxidised derivative of 5mC produced by the process of active DNA demethylation [4, 5]. Of note, 5hmC is present at relatively high levels in the mature central nervous system [6], and particularly enriched in the vicinity of genes with synapserelated functions [7]. Although initially hypothesized to represent an intermediate step of the DNA demethylation pathway, 5hmC is now assumed to have specific functional roles in the brain. Several specific molecular readers* Correspondence: [email protected] 2 University of Exeter Medical School, RILD Building, Royal Devon and Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK Full list of author information is available at the end of the articleof 5hmC have been identified, including transcriptional regulators, chromatin modifiers and DNA damage and repair proteins [8?2]. Additionally, the ten-eleven translocation (TET) family of proteins that catalyze the conversion of 5mC into 5hmC have been implicated in neuronal differentiation and function [13]; studies manipulating TET activity suggest that 5hmC plays a role in learning and memory, hippocampal neurogenesis, and neuronal activity-regulated gene expression [14?6]. Recently, 5hmC has been found to mark regulatory regions of the genome in the murine and human fetal brain [2, 17] and increase rapidly in abundance postnatally, concurrent with neuronal maturation and synaptogenesis [18?0]. Notably, there is growing evidence to suggest that abnormal regulation of 5hmC contributes to the etiology of several neurodevelopmental disorders including autism spectrum disorders [21] and schizophrenia [22]. Importantly, many of the standard methods used to quantify 5mC, including those based on sodium bisulfite (BS) conversion of DNA, are unable to discriminate between 5mC and 5hmC [10, 23], with important implications for the interpretation of published DNA methylation datasets from brain. Recently, a number of methods have?The Author(s). 2017 Open Access This article is distributed under the terms of the Nutlin (3a)MedChemExpress Nutlin-3a chiral Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27527552 medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Spiers et al. BMC Genomics (2017) 18:Page 2 ofbeen developed to enable the quantification of 5hmC across the genome [24]. Oxidative bisulfite (oxBS) conversion of genomic DNA, wh.
