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Methylomic trajectories across human fetal brain development

Spiers, Helen and Hannon, Eilis and Schalkwyk, Leonard C and Smith, Rebecca and Wong, Chloe CY and O’Donovan, Michael C and Bray, Nicholas J and Mill, Jonathan (2015) 'Methylomic trajectories across human fetal brain development.' Genome Research, 25 (3). pp. 338-352. ISSN 1088-9051

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Abstract

<jats:p>Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (<jats:italic>MECP2</jats:italic>) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at &gt;7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity.</jats:p>

Item Type: Article
Uncontrolled Keywords: Brain; Humans; Cluster Analysis; Gene Expression Profiling; Autistic Disorder; Schizophrenia; Sex Factors; DNA Methylation; Epigenesis, Genetic; Base Composition; CpG Islands; Regulatory Sequences, Nucleic Acid; Fetal Development; Organogenesis; Pregnancy; Female; Male; Genome-Wide Association Study; Epigenomics
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 23 Feb 2015 16:45
Last Modified: 18 Aug 2022 12:09
URI: http://repository.essex.ac.uk/id/eprint/13008

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