Nuclear architecture as an epigenetic regulator of neural development and function

• The nucleus is non-randomly organized into compartments and domains that impact genome function.
• Regulation of nuclear architecture accompanies neurogenesis and neuronal activity.
• Nuclear architecture could be a broad epigenetic regulator of neural cell diversity and function.

The nervous system of higher organisms is characterized by an enormous diversity of cell types that function in concert to carry out a myriad of neuronal functions. Differences in connectivity, and subsequent physiology of the connected neurons, are a result of differences in transcriptional programs. The extraordinary complexity of the nervous system requires an equally complex regulatory system. It is well established that transcription factor combinations and the organization of cis-regulatory sequences control commitment to differentiation programs and preserve a nuclear plasticity required for neuronal functions. However, an additional level of regulation is provided by epigenetic controls. Among various epigenetic processes, nuclear organization and the control of genome architecture emerge as an efficient and powerful form of gene regulation that meets the unique needs of the post-mitotic neuron. Here, we present an outline of how nuclear architecture affects transcription and provide examples from the recent literature where these principles are used by the nervous system.