Paradigms for establishing long-term epigenetic states in brain

Nature uses epigenetics to establish gene expression patterns in cells that, while reversible, are stable over the lifetime of an individual. If we could appropriately harness the rules of epigenetics, we should be able to use short-term interventions to create lifelong therapeutic effects on gene expression. Such epigenetic edits would be comparatively safer (compared to creating double-strand breaks), reversible, and potentially tunable. However, key challenges have impeded the realization of these ambitions in vivo , especially in the brain. Efforts to overcome these challenges have established the basic paradigms driving research and innovations over the past several years. This chapter will describe these basic paradigms and how they are being applied to achieve long-term epigenetic editing in the brains of animal models in vivo .