Whole-genome analysis of neural epigenomes
Recent advances in molecular biology/genetics reveal that variation in DNA methylation often occurs either in alternative forms of methylation, such as 5-hydroxymethylation, or at non-CpG sites. The exact function of these variants in relation to transcription is not clear, not do we know of the relative sensitivity of such variants to environmental influences. Moreover it is not clear how modifications to DNA methylation, in whatever form, align with histone modifications. Our current studies use next generation sequencing with microdissected brain samples and defined cellular populations to define the impact of ‘clinically-relevant’ environmental conditions across the genome using rodent models. A clinically-relevant condition is defined as one that mimics conditions that predict mental health outcomes in humans. Examples of this approach are studies of variations in maternal care or environmental enrichment/social isolation. Moreover, the use of genetically modified rodent models allows us to examine the influence of genotype on the effect of environmental conditions on specific epigenetic signals.
We currently collaborate with the McGill Centre for Innovation, which is linked to the International Human Epigenome Consortium (IHEC) to use state-of-the-art sequencing approaches to the study of coordinated epigenetic states in multiple brain regions. These studies permit the concurrent analysis of multiple forms of DNA methylation, histone PTMs and transcription. Studies with multiple transgenic models will permit the study of essential signaling pathways that link environmental conditions to epigenetic states. The Ludmer Centre for Neuroinformatics and Mental Health offers state-of-the-art bioinformatics support for the analysis of the resulting whole-genome sequencing data.