Nucleoporin-mediated regulation of cell identity genes

Ibarra, Arkaitz; Benner, Chris; Tyagi, Swati; Cool, Jonah; Hetzer, Martin W.

doi:10.1101/gad.287417.116

Cited by 145 publications

(165 citation statements)

References 40 publications

(66 reference statements)

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“…However, it has long been observed by electron microscopy that NPCs are surrounded by decondensed chromatin (Capelson and Hetzer, 2009; Lemaitre and Bickmore, 2015), suggesting the association of active genes or chromatin regions with NPCs and the potential role of these structures in positively regulating gene expression. Supporting this hypothesis, the association of super-enhancer sequences with NPCs was recently identified (Ibarra et al, 2016). …”

Section: Introductionmentioning

confidence: 73%

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

et al. 2017

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SUMMARY Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.

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Section: Introductionmentioning

confidence: 73%

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

et al. 2017

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“…In stark contrast, in two human cell lines Nup93 and Nup153 showed a tendency to interact with super-enhancer regions that are preferentially located near the nuclear periphery. Depletion of Nup153 and Nup93 resulted in transcriptional changes of the genes associated with these enhancers (Ibarra et al, 2016). …”

Section: Lads Do Not Appear To Be Linked To Nuclear Pore Complexesmentioning

confidence: 99%

Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression

Steensel

Belmont

2017

Cell

840

851

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In metazoan cell nuclei, hundreds of large chromatin domains are in close contact with the nuclear lamina. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. Here, we discuss the properties of LADs, the molecular mechanisms that determine their association with the nuclear lamina, their dynamic links with other nuclear compartments, and their proposed roles in gene regulation.

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Section: Box 1 Basic Organization Of Chromatin In the Nucleusmentioning

confidence: 99%

“…Genomic regions that interact with NPC proteins such as Nup153 and Nup93 are mainly comprised of gene enhancers and are closer to transcription start sites (Ibarra et al, 2016). Moreover, knockdown of Nup153 results in a change in expression of genes associated with enhancers that bind NPCs, suggesting that NPC proteins regulate the transcriptional activity of these genes in a selective manner (Ibarra et al, 2016). The importance of NPC proteins in controlling gene expression is also demonstrated by mutations in NPC components that alter the expression of genes and The mechanisms for anchoring lamin-associated domains (LADs) to the nuclear periphery in mammalian cells involve specific laminaassociating sequences (LASs), the nuclear factors Lap2β, histone deacetylase 3 (HDAC3) and the TF cKrox.…”

Section: Box 1 Basic Organization Of Chromatin In the Nucleusmentioning

confidence: 99%

Causes and consequences of nuclear gene positioning

Shachar

Misteli

2017

Journal of Cell Science

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The eukaryotic genome is organized in a manner that allows folding of the genetic material in the confined space of the cell nucleus, while at the same time enabling its physiological function. A major principle of spatial genome organization is the non-random position of genomic loci relative to other loci and to nuclear bodies. The mechanisms that determine the spatial position of a locus, and how position affects function, are just beginning to be characterized. Initial results suggest that there are multiple, gene-specific mechanisms and the involvement of a wide range of cellular machineries. In this Commentary, we review recent findings from candidate approaches and unbiased screening methods that provide initial insight into the cellular mechanisms of positioning and their functional consequences. We highlight several specific mechanisms, including tethering of genome regions to the nuclear periphery, passage through S-phase and histone modifications, that contribute to gene positioning in yeast, plants and mammals.

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Nucleoporin-mediated regulation of cell identity genes

Cited by 145 publications

References 40 publications

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression

Causes and consequences of nuclear gene positioning

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