Transcription and Motoneuron Size

Sato, Shoko; Burgess, S. B.; McIlwain, D. L.

doi:10.1046/j.1471-4159.1994.63051609.x

Cited by 43 publications

(39 citation statements)

References 36 publications

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“…We have taken advantage of the cell size heterogeneity of DRG neurons to demonstrate a correlation between the cell body mass and both nucleolar size and CB number. The cell body mass is positively related to transcription rate and metabolic activity in vertebrate neurons and in other diploid cell types (McIlwain, 1991;Sato et al, 1994;Schmidt and Schibler, 1995). In this sense, previous kinetic studies of uridine incorporation rate in RNA have demonstrated that the cell size correlates with RNA content and RNA:DNA ratio in cells from adult rodents (Schmidt and Schibler, 1995).…”

Section: Discussionmentioning

confidence: 98%

“…Type C neurons are the smallest ganglion cells, and give rise to largely unmyelinated and nociceptive Wbers (Hunt et al, 1992). These cell types of the DRG provide an excellent neuronal model of post-mitotic cells for studying the inXuence of cellular mass, a parameter directly related to global transcriptional activity (Sato et al, 1994;Schmidt and Schibler, 1995), on the organization of nuclear compartments involved in transcription and RNA processing.…”

Section: Introductionmentioning

confidence: 99%

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Cajal body number and nucleolar size correlate with the cell body mass in human sensory ganglia neurons

Berciano

Novell

Villagra

et al. 2007

Journal of Structural Biology

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Cajal body number and nucleolar size correlate with the cell body mass in human sensory ganglia neurons

Berciano

Novell

Villagra

et al. 2007

Journal of Structural Biology

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“…Because the nuclear volume was found to be invariant among cells of different shape and the strain along the two principal axes was equal, we considered the nucleus to be an ellipsoid with Young's modulus of the order of 5 KPa (1) and estimated the force required to change N pa by 25 ± 5% to be ∼10-15 nN. Simultaneously, a strong correlation was observed between nuclear volume and histone acetylation levels, suggesting that changes in nuclear morphology might enhance accessibility to transcriptional machinery and hence regulate total levels of transcription (39)(40)(41). We also show that the degree of actin polymerization and actomyosin contractility depends on cell geometry, consistent with a previous report that suggests that distribution of stress fibers was sensitive to geometry of underlying substrate (3).…”

Section: Discussionmentioning

confidence: 99%

Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility

Jain

Iyer

Kumar

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

326

312

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Physical forces in the form of substrate rigidity or geometrical constraints have been shown to alter gene expression profile and differentiation programs. However, the underlying mechanism of gene regulation by these mechanical cues is largely unknown. In this work, we use micropatterned substrates to alter cellular geometry (shape, aspect ratio, and size) and study the nuclear mechanotransduction to regulate gene expression. Genome-wide transcriptome analysis revealed cell geometry-dependent alterations in actin-related gene expression. Increase in cell size reinforced expression of matrix-related genes, whereas reduced cell-substrate contact resulted in up-regulation of genes involved in cellular homeostasis. We also show that large-scale changes in geneexpression profile mapped onto differential modulation of nuclear morphology, actomyosin contractility and histone acetylation. Interestingly, cytoplasmic-to-nuclear redistribution of histone deacetylase 3 modulated histone acetylation in an actomyosin-dependent manner. In addition, we show that geometric constraints altered the nuclear fraction of myocardin-related transcription factor. These fractions exhibited hindered diffusion time scale within the nucleus, correlated with enhanced serum-response element promoter activity. Furthermore, nuclear accumulation of myocardin-related transcription factor also modulated NF-κB activity. Taken together, our work provides modularity in switching gene-expression patterns by cell geometric constraints via actomyosin contractility.cell matrix interaction | substrate geometry | MRTF-A signaling | chromatin remodelling | transcription control C ells within the local tissue microenvironment acquire nonrandom geometrical organization by cell-matrix and cell-cell interaction. Cellular geometry has been shown to influence nuclear deformation, cytoskeleton reorganization, chromatin compaction, gene expression, growth, apoptosis, and cell division (1-7). Other physical cues such as substrate stretching, fluid flow, substrate rigidity, and cellular topography have also been shown to alter cellular morphology, nuclear architecture, and gene expression (8-11). Regulation of gene expression requires posttranslational modifications of histone tails (12), which alter higher-order chromatin assembly and, hence, the accessibility of gene-regulatory sites by transcriptional machinery (13). In addition, cytoplasmic to nuclear shuttling of transcription factors (TFs) and cofactors are key signaling intermediates rendering specificity. Some of these factors include NF-κB, STAT, and myocardin-related transcription factor (MRTF-A) (14-16). The transcription coactivator yes-associated protein (YAP)/transcription coactivator with PDZ binding domain (TAZ) and MRTF-A have been implicated in nuclear mechanotransduction (17)(18)(19). In a recent study, alterations in cell shape were shown to influence mesenchymal stem cell differentiation (20). However, the mechanisms underlying geometric control of gene expression by the modulation of cytoplasmi...

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“…In addition, a strong correlation between nuclear size, RNA transcription levels and cell size has been found (e.g. Sato et al, 1994;Schmidt and Schibler, 1995). It is therefore possible that larger nuclei facilitate the increase in transcription that is required in larger cells.…”

Section: Does Size Matter For Nuclear Function?mentioning

confidence: 99%

Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly

Webster

Witkin

Cohen-Fix

2009

Journal of Cell Science

389

342

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The nucleus is one of the most prominent cellular organelles, yet surprisingly little is known about how it is formed, what determines its shape and what defines its size. As the nuclear envelope (NE) disassembles in each and every cell cycle in metazoans, the process of rebuilding the nucleus is crucial for proper development and cell proliferation. In this Commentary, we summarize what is known about the regulation of nuclear shape and size, and highlight recent findings that shed light on the process of building a nucleus, including new discoveries related to NE assembly and the relationship between the NE and the endoplasmic reticulum (ER). Throughout our discussion, we note interesting aspects of nuclear structure that have yet to be resolved. Finally, we present an idea -which we refer to as 'the limited flat membrane hypothesis' -to explain the formation of a single nucleus that encompasses of all of the cell's chromosomes following mitosis. Nuclear shapeThe nuclei of most cells are either round or oval. This, in itself, is hardly remarkable except for the fact that various diseases, as well as aging, are associated with alterations in nuclear shape (Fig. 3). Moreover, in certain specialized cell types, altered nuclear shape is important for cell function. But what determines nuclear shape, and how does shape affect function? In many cell types, altered nuclear shape is due to changes in the nuclear lamina. In some cases, however, the shape of the nucleus is altered by forces that act from the cytoplasm. In either case, it is still not entirely clear how nuclear shape affects function, although two main hypotheses exist. The first hypothesis posits that changes in nuclear shape alter the rigidity of the nucleus; this could be beneficial for cells that need to squeeze through tight spaces, but deleterious to cells that are under mechanical duress. The second hypothesis proposes that changes in nuclear shape result in chromatin reorganization and thereby affect gene expression. It is important to note that these two hypotheses are not mutually exclusive. In addition, because nuclear shape changes are often accompanied by an altered nuclear lamina, it is possible that the dramatic effect on cell function is due to aberrant properties of the lamina rather than nuclear shape changes per se. In this section, we examine some of the cell types and conditions that are associated with irregular nuclear shape, and we discuss, when known, the causes of these shape changes and how they affect cell function. Normal cells with abnormal nucleiOf all the cell types that normally exhibit unusual nuclear shape, neutrophils have been studied the most thoroughly. Neutrophils are cells of the immune system that migrate through tissue towards sites of infection. They are characterized by their multi-lobed nuclei, typically exhibiting three or four lobes that are connected by thin DNA-containing filaments ( Fig. 3B) (reviewed by Hoffmann et al., 2007). Neutrophils with hypolobulated nuclei are associated with Pelger-Huet anoma...

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Transcription and Motoneuron Size

Cited by 43 publications

References 36 publications

Cajal body number and nucleolar size correlate with the cell body mass in human sensory ganglia neurons

Cajal body number and nucleolar size correlate with the cell body mass in human sensory ganglia neurons

Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility

Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly

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