Epigenetic priming in neurodevelopmental disorders

Abstract

Neurodevelopmental disorders (NDDs) affect about 1% of the population and can be caused by mutations in genes that affect the epigenetic code. There is limited functional understanding of most of these epigenetic modifiers, and we suggest that associated NDDs are caused, in part, by deficits in epigenetic priming, a prepatterning step that alters the genome in preparation to make cells competent to signaling cues. We provide evidence from high-resolution epigenetic and transcriptomic mapping studies to demonstrate how a failure to adequately prime the genome for neural induction could lead to impairment of terminally differentiated cells. This idea provides a framework for NDD pathogenesis and treatment.

Keywords: Kabuki syndrome; epigenetic priming; histone modifications; neurodevelopmental disorders.