Editorial overview: Cell nucleus: The nucleus: a dynamic organelle Michael P Rout and Gary H Karpen Current Opinion in Structural Biology 2014, 28:iv–vii For a complete overview see the Issue Available online 4th June 2014 http://dx.doi.org/10.1016/j.ceb.2014.05.005 0955-0674/Published by Elsevier Ltd. The nucleus is perhaps the defining feature of ‘eukaryotes’ (Greek ‘eu-’ (with) ‘-karyon’ (kernel, nucleus)), and the emperor of all eukaryotic organelles in terms of scale and complexity of organization. It is, of course, the repository for almost all genomic information, encoded in DNA sequences wrapped into chromatin as discrete polymer packages termed chromosomes, surrounded in turn by a double-membrane nuclear envelope (NE). Our investment in genomics in humans and other eukaryotes has been rightly huge; however, the return has been slow, as we discovered that sequence assemblies alone reveal little about how genetic information is utilized. Instead, genome functions are greatly influenced by processes that control nuclear and chromosome architecture and dynamics — chromatin factors and modifications, epigenetic mechanisms, and pathways for con- trolling transport of molecules into and out of the nucleus. Moreover, the genome is not just a computer that reads software — rather, in the nucleus we cannot separate the control system from the machinery. For example, DNA not only provides the genetic code but also forms the dynamic scaffold for nuclear structures, and the way chromatin packaging proteins are modified can also be part of the heritable code. A huge portion of the eukaryotic cellular machinery is involved in nuclear maintenance and function, such that likely over one-third of all proteins, and almost all RNA and DNA, make the nucleus an integral part of their lifestyle in the cell. Therefore, if we ever want a full return on our investment, we must now devote resources to fully understand how the nucleus functions as an organelle, actively manages the hierarchical organization, expression, and communication across the genome, in both healthy and diseased cells. The Opinions here reflect this changing view of the nucleus as an organelle; not a passive repository for genetic information, but an active, dynamic super- structure whose processes dictate how that information is organized, accessed and used. The Opinions presented here consider recent findings on the spatial and temporal organization of chromatin, the structure and dynamic organization of the nuclear periphery, and the mechanisms and regulation of nucleocy- toplasmic exchange. As reflected in these various articles, our understanding of the architecture of the nucleus, specifically the 3D localization of genomic regions, whole chromosome and sub-chromosome domains, and nuclear bodies or ‘factories’ associated with transcription, replication and DNA repair, has advanced considerably in recent years due to important techno- logical advances. They also discuss how many parts of the nucleus have multiple and dynamically changing functionalities, involving the rapid Michael P Rout Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, United States e-mail: rout@mail.rockefeller.edu Michael P Rout received his Ph.D. in 1990 from the Medical Research Council Laboratory of Molecular Biology at the University of Cambridge, working with John Kilmartin. He joined Rockefeller in 1990 as a postdoctoral fellow in Gu ¨ nter Blobel’s laboratory and was appointed assistant professor and head of laboratory in 1997 and professor in 2008. Gary H Karpen Life Sciences Division, Lawrence Berkeley National Lab, and Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, United States e-mail: ghkarpen@lbl.gov Gary H Karpen is the Director of Berkeley Lab Life Sciences Division. He received his PhD from the University of Washington, Department of Genetics, in 1987. He performed postdoctoral work with Allan Spradling at the Carnegie Institute, and was on the faculty at The Salk Institute (La Jolla) from 1991 to 2003, before moving to LBNL and UC Berkeley. Available online at www.sciencedirect.com ScienceDirect Current Opinion in Cell Biology 2014, 28:iv–vii www.sciencedirect.com