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Spatial Organization of the Nucleus Compartmentalizes and Regulates the Genome

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Nuclear Pore Complexes in Genome Organization, Function and Maintenance

Abstract

The nucleus must simultaneously orchestrate DNA replication, transcription, splicing, signalling, and directional transport of proteins into the nucleus and RNA out of the nucleus. Yet the nucleus has no internal membranes to compartmentalize these functions as the cytoplasm does. In fact, such compartmentalization would necessarily be detrimental because particular genes at different locations on the linear chromosomes need to be made at different times while others on the same chromosome need to be tightly shut off. Moreover, expressed genes need to be accessible to a feedback mechanism to determine when to modulate transcription. To accommodate these additional needs the nucleus appears to form microdomains by co-assembly of functional complexes. Thus, microdomains can either form around activated regions on a chromosome or regions on a linear chromosome could be fed into such microdomains for activation. Findings that genome encoded regulatory elements such as enhancers can be hundreds of kb and even Mb apart further highlights the need for such a system as these distal elements must come together in the 3D space of the genome for their efficient functioning. While this much is understood, there is much still to be learned about mechanisms that the nucleus uses to regulate the genome and much more to be learned about how these microdomains come into being. As there is no stable structure within the nucleus except for the nuclear envelope, much recent research has been focusing on potential roles of this subnuclear organelle in establishing 3D nuclear architecture and orchestrating the regulation of these various functions.

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Correspondence to Eric C. Schirmer .

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Robson, M.I., Rizzotto, A., Schirmer, E.C. (2018). Spatial Organization of the Nucleus Compartmentalizes and Regulates the Genome. In: D’Angelo, M. (eds) Nuclear Pore Complexes in Genome Organization, Function and Maintenance. Springer, Cham. https://doi.org/10.1007/978-3-319-71614-5_1

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