Role of the nuclear envelope in genome organization and gene expression

Department of Cell Biology, University of Alberta, Edmonton, AB, Canada.
Wiley Interdisciplinary Reviews Systems Biology and Medicine (Impact Factor: 3.21). 03/2011; 3(2):147-66. DOI: 10.1002/wsbm.101
Source: PubMed


Although often depicted as a static structure upon which proteinaceous factors bind to control gene expression, the genome is actually highly mobile and capable of exploring the complex domain architecture of the nucleus, which in turn controls genome maintenance and gene expression. Numerous genes relocate from the nuclear periphery to the nuclear interior upon activation and are hypothesized to interact with pre-assembled sites of transcription. In contrast to the nuclear interior, the nuclear periphery is widely regarded as transcriptionally silent. This is reflected by the preferential association of heterochromatin with the nuclear envelope (NE). However, some activated genes are recruited to the nuclear periphery through interactions with nuclear pore complexes (NPCs), and NPC components are capable of preventing the spread of silent chromatin into adjacent regions of active chromatin, leading to the speculation that NPCs may facilitate the transition of chromatin between transcriptional states. Thus, the NE might better be considered as a discontinuous platform that promotes both gene activation and repression. As such, it is perhaps not surprising that many disease states are frequently associated with alterations in the NE. Here, we review the effects of the NE and its constituents on chromatin organization and gene expression. WIREs Syst Biol Med 2011 3 147–166 DOI: 10.1002/wsbm.101
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    • "Differentiated muscle cells uniquely express gp210 at the NPC leading to activation of muscle specific genes. been implicated in a number of chromatin-associated processes (Akhtar and Gasser, 2007; Arib and Akhtar, 2011; Van de Vosse et al., 2011; Amendola and van Steensel, 2014). While several of these processes have been characterized individually , how nuclear components work together to execute tissue specific gene expression programs is still unclear. "
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    ABSTRACT: The eukaryotic cell nucleus houses an organism's genome and is the location within the cell where all signaling induced and development-driven gene expression programs are ultimately specified. The genome is enclosed and separated from the cytoplasm by the nuclear envelope (NE), a double-lipid membrane bilayer, which contains a large variety of trans-membrane and associated protein complexes. In recent years, research regarding multiple aspects of the cell nucleus points to a highly dynamic and coordinated concert of efforts between chromatin and the NE in regulation of gene expression. Details of how this concert is orchestrated and how it directs cell differentiation and disease are coming to light at a rapid pace. Here we review existing and emerging concepts of how interactions between the genome and the NE may contribute to tissue specific gene expression programs to determine cell fate.
    Frontiers in Genetics 03/2015; 6:95. DOI:10.3389/fgene.2015.00095
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    • "It is still uncertain how NPC components could modulate gene expression, but it has been proposed that Nups might mediate this function by influencing the chromatin landscape. Indeed, the NE, as the largest physical scaffold of the nucleus, has been historically suggested to influence the nonrandom organization of the eukaryotic chromosomes and thus their functions (Akhtar and Gasser 2007; Mekhail and Moazed 2010; Van de Vosse et al. 2011). High-resolution images of the nuclear structure of different mammalian cell types revealed that the NE is underlain by the nuclear lamina, an intermediate filament structure that generally associates with heterochromatin, interrupted by decondensed euchromatin patches under the NPCs (Belmont et al. 1993; Schermelleh et al. 2008). "
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    Genes & Development 02/2015; 29(4):337-349. DOI:10.1101/gad.256495.114 · 10.80 Impact Factor
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    • "The importance of these NR structures for chromosome partitioning, nuclear transport, gene expression, or other cellular processes are not well understood. Although we lack a comprehensive understanding of the functional role of nuclear architecture, it has become clear that the nuclear envelope and its three-dimensional shape can profoundly impact genome organization and gene expression (De Vosse et al. 2011; Schneider and Grosschedl 2007). The typical interphase genome is radially organized with heterochromatin and transcriptionally silent gene regions predominantly restricted to the nuclear periphery (Hochstrasser and Sedat 1987; Rajapakse and Groudine 2011). "
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    ABSTRACT: Although the nuclear envelope is primarily known for its role as a boundary between the nucleus and cytoplasm in eukaryotes, it plays a vital and dynamic role in many cellular processes. Studies of nuclear structure have revealed tissue specific changes in nuclear envelope architecture, suggesting that its three-dimensional structure contributes to its functionality. Despite the importance of the nuclear envelope, the factors that regulate and maintain nuclear envelope shape remain largely unexplored. The nuclear envelope makes extensive and dynamic interactions with the underlying chromatin. Given this inexorable link between chromatin and the nuclear envelope, it is possible that local and global chromatin organization reciprocally impact nuclear envelope form and function. In this study, we use Drosophila salivary glands to show that the three-dimensional structure of the nuclear envelope can be altered with condensin II-mediated chromatin condensation. Both naturally occurring and engineered chromatin-envelope interactions are sufficient to allow chromatin compaction forces to drive distortions of the nuclear envelope. Weakening of the nuclear lamina further enhanced envelope remodeling, suggesting that envelope structure is capable of counterbalancing chromatin compaction forces. Our experiments reveal that the nucleoplasmic reticulum is born of the nuclear envelope and remains dynamic, in that they can be reabsorbed into the nuclear envelope. We propose a model where inner nuclear envelope-chromatin tethers allow interphase chromosome movements to change nuclear envelope morphology. Therefore, interphase chromatin compaction may be a normal mechanism that reorganizes nuclear architecture, while under pathological conditions, such as laminopathies, compaction forces may contribute to defects in nuclear morphology. Copyright © 2014 Author et al.
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