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: 3.01). 03/2011; 3(2):147-66. DOI: 10.1002/wsbm.101
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Richard W Wozniak, Jul 21, 2015
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    G3-Genes Genomes Genetics 12/2014; 5(3). DOI:10.1534/g3.114.015685 · 2.51 Impact Factor
  • Source
    • "The association of genomic regions with the nuclear lamina is dynamic in response to differentiation cues and external stimuli (Mehta et al. 2010; Peric-Hupkes et al. 2010). These dynamics are accompanied by coordinate changes in chromatin modifications consistent with transcriptional activation upon dissociation from the lamina (Kind et al. 2013; Peric-Hupkes and van Steensel 2011). Multiple lines of evidence support emerin's role in regulating chromatin architecture at the nuclear lamina. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The spatial organization of chromatin is critical in establishing cell-type dependent gene expression programs. The inner nuclear membrane protein emerin has been implicated in regulating global chromatin architecture. We show emerin associates with genomic loci of muscle differentiation promoting factors in murine myogenic progenitors, including Myf5 and MyoD. Prior to their transcriptional activation Myf5 and MyoD loci localized to the nuclear lamina in proliferating progenitors and moved to the nucleoplasm upon transcriptional activation during differentiation. The Pax7 locus, which is transcribed in proliferating progenitors, localized to the nucleoplasm and Pax7 moved to the nuclear lamina upon repression during differentiation. Localization of Myf5, MyoD, and Pax7 to the nuclear lamina and proper temporal expression of these genes required emerin and HDAC3. Interestingly, activation of HDAC3 catalytic activity rescued both Myf5 localization to the nuclear lamina and its expression. Collectively, these data support a model whereby emerin facilitates repressive chromatin formation at the nuclear lamina by activating the catalytic activity of HDAC3 to regulate the coordinated spatiotemporal expression of myogenic differentiation genes.
    Chromosome Research 09/2013; 21(8). DOI:10.1007/s10577-013-9381-9 · 2.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The nucleocytoplasmic partitioning of nanoparticles as a result of cell division is highly relevant to the field of nonviral gene delivery. We reviewed the literature on the intracellular distribution of cell organelles (the endosomal vesicles, Golgi apparatus, endoplasmic reticulum and nucleus), foreign macromolecules (dextrans and plasmid DNA) and inorganic nanoparticles (gold, quantum dot and iron oxide) during mitosis. For nonviral gene delivery particles (lipid- or polymer-based), indirect proof of nuclear entry during mitosis is provided. We also describe how retroviruses and latent DNA viruses take advantage of mitosis to transfer their viral genome and segregate their episomes into the host daughter nuclei. Based on this knowledge, we propose strategies to improve nonviral gene delivery in dividing cells with the ultimate goal of designing nonviral gene delivery systems that are as efficient as their viral counterparts but non-immunogenic, non-oncogenic and easy and inexpensive to prepare.
    Advanced drug delivery reviews 12/2011; 64(1):78-94. DOI:10.1016/j.addr.2011.11.012 · 12.71 Impact Factor
Show more