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BMC Genomics. 2017 Sep 18;18(1):738. doi: 10.1186/s12864-017-4091-x.

5-hydroxymethylcytosine is highly dynamic across human fetal brain development.

Author information

1
Department of Physics, University of Oxford, Oxford, OX1 3RH, UK.
2
University of Exeter Medical School, RILD Building, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
3
School of Biological Sciences, University of Essex, Colchester, CO4 3SQ, UK.
4
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, CF24 4HQ, UK.
5
University of Exeter Medical School, RILD Building, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK. j.mill@exeter.ac.uk.

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 .

PMID:
28923016
PMCID:
PMC5604137
DOI:
10.1186/s12864-017-4091-x
[Indexed for MEDLINE]
Free PMC Article

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