Epigenetics of Circadian Rhythms in Imprinted Neurodevelopmental Disorders

DNA sequence information alone cannot account for the immense variability between chromosomal alleles within diverse cell types in the brain, whether these differences are observed across time, cell type, or parental origin. The complex control and maintenance of gene expression and modulation are regulated by a multitude of molecular and cellular mechanisms that layer on top of the genetic code. The integration of genetic and environmental signals required for regulating brain development and function is achieved in part by a dynamic epigenetic landscape that includes DNA methylation, histone modifications, and noncoding RNAs. These epigenetic mechanisms establish and maintain core biological processes, including genomic imprinting and entrainment of circadian rhythms. This chapter will focus on how the epigenetic layers of DNA methylation and long, noncoding RNAs interact with circadian rhythms at specific imprinted chromosomal loci associated with the human neurodevelopmental disorders Prader-Willi, Angelman, Kagami-Ogata, and Temple syndromes.