Identifying single-molecule epigenetic modification patterns regulating age-associated neuroinflammatory gene expression programs
Every cell in an individual shares the same genetic code. Epigenetic modifications mark the invariant genetic code with plastic information that defines cell identity by modulating gene expression. Changes to epigenetic modifications correlate with aging, and “epigenetic clocks” use modifications to predict chronological age. However, current methods focus on averaged epigenetic modification levels at specific sites or regions of the genome across populations of cells, so we have not resolved long-range epigenetic modification patterns that determine cell identity. Dr. Hoolehan's work will identify epigenetic modification patterns regulating nervous system cell-type specific gene expression programs, how these epigenetic programs change during aging, and determine if cell-type specific changes to epigenetic modification patterns correlate with cognitive dysfunction and age-associated inflammation in the brain. These studies will help determine whether deleterious, age-associated alterations to the neuroepigenomic landscape are primarily adaptive programs within specific cell types, or stochastic changes accumulated during aging.
