The nuclei of differentiating cells exhibit several fundamental principles of self‐organization. They are composed of many dynamical units connected physically and functionally to each other—a complex network—and the different parts of the system are mutually adapted and produce a characteristic end state. A unique cell‐specific signature emerges over time from complex interactions among constituent elements that delineate coordinate gene expression and chromosome topology. Each element itself consists of many interacting components, all dynamical in nature. Self‐organizing systems can be simplified while retaining complex information using approaches that examine the relationship between elements, such as spatial relationships and transcriptional information. These relationships can be represented using well‐defined networks. We hypothesize that during the process of differentiation, networks within the cell nucleus rewire according to simple rules, from which a higher level of order emerges. Studying the interaction within and among networks provides a useful framework for investigating the complex organization and dynamic function of the nucleus.