8 Fig. 2 Intranuclear compart- ments. The mammalian cell nu- cleus contains a larger number of distinct intranuclear compart- ments. The nucleolus is the site of ribosomal RNA synthesis and is a prototypical nuclear body. The complex organization of the nucleolus is revealed by multi- color staining of distinct nucleo- lar components. RPA43 RNA polymerase I transcription fac- tor, Fibrillarin snRNP compo- nent, B23 rRNA processing factor. Image courtesy of Miro- slav Dundr, Rosalind Franklin University of Medicine and Sci- ence, Chicago Histochem Cell Biol (2008) 129:5–11 include splicing factor compartments which serve as stor- age and assembly sites for spliceosomal components, and the Cajal bodies which are possibly involved in maturation of small nuclear RNPs. The structure of intranuclear bodies is not determined by a membrane, and the principles under- lying their biogenesis are extremely poorly understood. The recently revealed dynamic properties of proteins in nuclear compartments give a hint as to the principles involved in subnuclear compartment assembly. The key property in understanding the formation of nuclear compartment is the remarkable fact that the asso- ciation of proteins with their compartments is highly dynamic (Dundr et al. 2004; Kruhlak et al. 2000; Phair and Misteli 2000). Typical residence times of proteins within a compartment are in the seconds range. In practical terms the dynamic behavior of nuclear body proteins means that they undergo repeated rapid cycles of association and dis- sociation between the nuclear body and the nucleoplasm. As a consequence, a nuclear body is in perpetual Xux and its structure is determined by the ratio of on-rate versus oV- rate of its proteins. Given these observations, the simplest scenario to explain the formation of nuclear subdomains is a self-orga- nization model in which the collective sum of all inter- actions amongst proteins in a body establishes and determines its structure (Carrero et al. 2006; Misteli 2007). In this model, nuclear bodies are essentially dynamic pro- tein aggregates which form as a consequence of multiple, transient interactions amongst a large number of proteins. This is consistent with the lack of deWning intranuclear 123 membranes and with the absence of any known dedicated structural elements within intranuclear bodies. While dynamic observations on nucleoli, splicing factor compart- ments and Cajal bodies support this view, this model has not been rigorously tested experimentally. A key predic- tion, and a way to experimentally address this fundamental question, is that it should be possible to create nuclear bod- ies de novo and that any nuclear body component should be able to nucleate the formation of a body. Experimental sys- tems to test these predictions are now available, and we are eagerly awaiting the results of these key experiments. The importance of protein and RNA dynamics in regulatory events The observation of dynamic properties of proteins in the cell nucleus of living cells has suggested that dynamic traYcking is an intrinsic property of proteins and RNAs. The dynamic behavior of proteins and RNAs clearly con- tributes to their proper function. However, is dynamic traYcking important for physiological regulation? Several observations demonstrate that dynamic traYcking of both proteins and RNA indeed can have regulatory function by several means. Of particular importance as a regulatory mechanism is intranuclear sequestration (Fig. 3). Accumulation of a pro- tein at a particular nuclear site or within a nuclear compart- ment can serve to either increase the local concentration of a factor at that site or to reduce its abundance in the rest of