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      5-hydroxymethylcytosine is highly dynamic across human fetal brain development

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      Date
      2017-09-18
      Author
      Spiers, H
      Hannon, EJ
      Schalkwyk, LS
      Bray, NJ
      Mill, J
      Date issued
      2017-09-18
      Journal
      BMC Genomics
      Type
      Article
      Language
      en
      Publisher
      BioMed Central
      Rights
      © The Author(s). 2017. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any 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.
      Abstract
      Background Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory. In this study, we quantify 5hmC across the genome of 71 human fetal brain samples spanning 23 to 184 days post-conception. Results We identify widespread changes in 5hmC occurring during human brain development, notable sex-differences in 5hmC in the fetal brain, and interactions between 5mC and 5hmC at specific sites. Finally, we identify loci where 5hmC in the fetal brain is associated with genetic variation. Conclusions This study represents the first systematic analysis of dynamic changes in 5hmC across human neurodevelopment and highlights the potential 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.
      Funders/Sponsor
      This project was supported by a Brain & Behavior Research Foundation Distinguished Investigator Award to J.M. H.S. was supported by an MRC PhD studentship. The human embryonic and fetal material was provided by the Joint MRC (grant #G0700089)/Wellcome Trust (grant #GR082557) Human Developmental Biology Resource (http://www.hdbr.org).
      Description
      This is the final version of the article. Available from BioMed Central via the DOI in this record.
      Citation
      Vol. 18, article 738
      DOI
      https://doi.org/10.1186/s12864-017-4091-x
      URI
      http://hdl.handle.net/10871/29417
      ISSN
      1471-2164
      Collections
      • Institute of Biomedical & Clinical Science

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