If variety is the spice to life than the brain must be the spiciest organ of them all, with DNA methylation as its rooster sauce (which comes with its own embedded sodium bisuflite conversion kit). By studying the delicious layers of DNA methylation variation we’ve seen strange parental expression biases, methylation differences between discordant twins, and how the dynamics of normal neurodevelopment relate as a proxy to peripheral tissue. And now profiling DNA methylation variation can bridge the translational gap by providing solid evidence for the relationship between individual variation, sex, and the developmental origin of diseases, like schizophrenia.
Researchers from the Lab of Jonathan Mill at King’s College London and the University of Exeter Medical School are at it again with yet another big contribution to our understanding of the methylomics of neurodevelopment. In their latest study the researchers examine the methylome of 179 human fetal brain samples (100 male, 79 female) during neurodevelopment (23–184 days post-conception).
Here’s what they found:
- The methylation change is widespread: 7% of the ~400,000 CpGs show hypo- or hyper-methylation that is related to fetal age.
- These sites show interesting CpG density related distributions. They are underrepresented in promoter regulatory regions, such as CpG islands, but are interestingly overrepresented in the flanking regions: CpG shores and shelves, and gene bodies.
- There is a significant reduction in non-CpG methylation at several locations throughout fetal brain development.
- Sex differences were observed between males and females not just in the sex chromosomes, but also in the autosomes, with some even showing sex specific developmental trajectories.
- The discrete modules of comethylated loci associated with age are enriched for genes that are functionally related to neurodevelopment and often show up in studies on schizophrenia and autism.
Ultimately, this research offers the most comprehensive look available at the dynamics of methylation across human fetal development, demonstrating the large scale epigenomic plasticity of neurodevelopment.
Senior author Jonathan Mill shares that “The prenatal period is a time of dramatic plasticity, when the brain is laying down the structures that control neurobiological function across life. Understanding the way in which genes are activated during this important period in the brain could teach us about the origins of disorders with a neurodevelopmental component, such as autism and schizophrenia.” Lead author Helen Spiers concludes with her insight that “Males and females show differences in their susceptibility to some neurological conditions. For example, autism affects five males to every female. Understanding sex differences in brain development may help us understand the origins of these differences.”
Go and wrap your brain around the trajectories in Genome Research, February 2015 and check out the methylomic trajectories of your favourite genes in the accompanying database.