Salk Institute for Biological Studies

The human genome sequence lists every DNA base of the roughly 3 billion bases that makes up the genome, but it doesn’t tell us about how its function is regulated.  That job belongs to the epigenome, the layer of genetic control beyond the regulation inherent in the sequence of the genes themselves.  Methylation of DNA at the carbon 5 position of cytosines constitutes an important epigenetic layer that contributes to the definition of transcriptional and regulatory potential of the genome.  DNA methylation in cells dynamically changes during aging and is susceptible to environmental influences.  To shed light on the dynamic variation of these marks in normal and diseased cells, novel technologies must be developed for the creation of base resolution maps of DNA methylation in single cells.  The interdisciplinary team proposes to develop an approach to “read the epigenome” information from single chromosomes within single neurons.  Being able to study DNA methylation in its entirety in single cells will greatly increase our understanding of how gene expression is influenced by the environment, including the impact of diet and stress, as well as how genome function is regulated in health but dysfunctional in disease states such as schizophrenia and other mental disorders.