Randomness of spatial distributions of two proteins in the cell nucleus involved in mRNA synthesis and their relationship

Noordmans, Herke Jan; Kraan, K. van der; Driel, Roel van; Smeulders, A.W.M.

doi:10.1002/(sici)1097-0320(19981101)33:3<297::aid-cyto3>3.0.co;2-e

Cited by 11 publications

(13 citation statements)

References 21 publications

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“…Nearest neighbor distances (G-function) have been used to characterize the spatial distribution of transcription factors [47], [48], [81], centromeres [49], and other nuclear compartments [82]. The distribution of all inter-distances (quantified through the pair correlation function or the K- and L-functions) has also been considered [49], [81]. To our knowledge, the present study is the first to rely on the F-function (the cumulative distribution of the distance from arbitrary nuclear positions to the nearest centromere/chromocenter) to investigate nuclear architecture.…”

Section: Discussionmentioning

confidence: 99%

“…For the G-function, for example, the Hanisch correction [87] consists in discarding the recorded points whose nearest neighbor is farther than the boundary. Such standard estimation corrections have been applied in studies on nuclear patterns [49], [81]. In this context, however, no point (here, centromere or chromocenter) is expected outside the nucleus.…”

Section: Discussionmentioning

confidence: 99%

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Statistical Analysis of 3D Images Detects Regular Spatial Distributions of Centromeres and Chromocenters in Animal and Plant Nuclei

Andrey

Kiêu

Kress³

et al. 2010

PLoS Comput Biol

108

119

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In eukaryotes, the interphase nucleus is organized in morphologically and/or functionally distinct nuclear “compartments”. Numerous studies highlight functional relationships between the spatial organization of the nucleus and gene regulation. This raises the question of whether nuclear organization principles exist and, if so, whether they are identical in the animal and plant kingdoms. We addressed this issue through the investigation of the three-dimensional distribution of the centromeres and chromocenters. We investigated five very diverse populations of interphase nuclei at different differentiation stages in their physiological environment, belonging to rabbit embryos at the 8-cell and blastocyst stages, differentiated rabbit mammary epithelial cells during lactation, and differentiated cells of Arabidopsis thaliana plantlets. We developed new tools based on the processing of confocal images and a new statistical approach based on G- and F- distance functions used in spatial statistics. Our original computational scheme takes into account both size and shape variability by comparing, for each nucleus, the observed distribution against a reference distribution estimated by Monte-Carlo sampling over the same nucleus. This implicit normalization allowed similar data processing and extraction of rules in the five differentiated nuclei populations of the three studied biological systems, despite differences in chromosome number, genome organization and heterochromatin content. We showed that centromeres/chromocenters form significantly more regularly spaced patterns than expected under a completely random situation, suggesting that repulsive constraints or spatial inhomogeneities underlay the spatial organization of heterochromatic compartments. The proposed technique should be useful for identifying further spatial features in a wide range of cell types.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Statistical Analysis of 3D Images Detects Regular Spatial Distributions of Centromeres and Chromocenters in Animal and Plant Nuclei

Andrey

Kiêu

Kress³

et al. 2010

PLoS Comput Biol

108

119

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“…The question arises of what the basis is for the cluster integrity. In another example, transcriptional regulators exist in many hundred smaller nuclear foci that occur both in association and away from chromatin (van Steensel et al, 1995;Grande et al, 1997;Hendzel et al, 1998;Noordmans et al, 1998) presence of a protein architecture to organize these factors into the domains observed in both fixed (van Steensel et al, 1995;Grande et al, 1997) and unfixed cells (Htun et al, 1996;Misteli et al, 1997;Fejes-Toth et al, 1998;Sleeman et al, 1998; Hendzel, Bisgrove, and Godbout, unpublished observations). A nucleus that spatially organizes biomolecules through specialization on an underlying architecture may be fundamentally different in the mechanisms that serve to transcribe, replicate, and repair DNA, process and export RNA, and transduce signals from that of a nucleus that is not ordered beyond the folding of chromatin.…”

Section: Introductionmentioning

confidence: 99%

“…Most biomolecules show some degree of spatial sequestration. These include transcription factors (van Steensel et al, 1995;Htun et al, 1996;Grande et al, 1997;Zeng et al, 1997;Fejes-Toth et al, 1998;Noordmans et al, 1998), RNA-processing machinery (for review, see Spector, 1993), and interphase chromosomes (for review, see Lamond and Earnshaw, 1998). More recently, the study of biomolecular organization in living cells, using fluorescence microscopy, has further indicated the presence of a component of the cell nucleus that is capable of spatially restricting the movement of biomolecular structures within the cell nucleus.…”

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confidence: 99%

Direct Visualization of a Protein Nuclear Architecture

Hendzel

Boisvert

Bazett-Jones

1999

MBoC

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Whether the cell nucleus is organized by an underlying architecture analagous to the cytoskeleton has been a highly contentious issue since the original isolation of a nuclease and salt-resistant nuclear matrix. Despite electron microscopy studies that show that a nuclear architecture can be visualized after fractionation, the necessity to elute chromatin to visualize this structure has hindered general acceptance of a karyoskeleton. Using an analytical electron microscopy method capable of quantitative elemental analysis, electron spectroscopic imaging, we show that the majority of the fine structure within interchromatin regions of the cell nucleus in fixed whole cells is not nucleoprotein. Rather, this fine structure is compositionally similar to known protein-based cellular structures of the cytoplasm. This study is the first demonstration of a protein network in unfractionated and uninfected cells and provides a method for the ultrastructural characterization of the interaction of this protein architecture with chromatin and ribonucleoprotein elements of the cell nucleus. INTRODUCTIONThe presence of an organizing principal within the cell nucleus that is analagous to the cytoskeleton has been hotly contested over the years. Recently, it has become practical to study directly the dynamics and motion of chromatin and nonchromatin elements of the cell nucleus. Consequently, in the absence of a convincing demonstration of a nuclear skeleton within unfractionated nuclei, it is possible to determine whether biomolecules behave as if they are embedded in an organizing supramolecular structure or whether they are subject to substantial Brownian motion. The results of such studies are compelling. Chromatin (Abney et al., 1997;Marshall et al., 1997;Kanda et al., 1998;Zink et al., 1998;Sullivan et al., 1999) and nonchromatin structures such as nuclear speckles (Misteli et al., 1997) and foci enriched in transcription factors (Hendzel, Bisgrove, and Godbout, unpublished observations) are constrained from substantial Brownian motion, strongly supporting the view that there is a component or components of the cell nucleus that function to restrict the mobility of macromolecular complexes within the cell nucleus.The cell nucleus has a number of compositionally distinct domains (for review, see Schul et al., 1998). This implies a mechanism for organizing biochemical components into discrete supramolecular structures. An example is the nonchromatin extranucleolar structure of the cell nucleus called the interchromatin granule cluster (IGC). This structure is more widely known by the nuclear speckles that are observed by indirect immunofluorescence when cells are stained with antibodies recognizing small nuclear ribonuclear proteins (RNPs) or SC-35 (for review, see Spector, 1993). The well-defined boundaries of nuclear speckles, when imaged by indirect immunofluorescence, indicates that they are discrete nuclear structures. Their large dimensions indicate that a physical continuity is maintained over relatively long distance...

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“…1). Another prominent feature of nuclear organization is the nonrandom localization of chromosome territories and protein domains (Noordmans et al, 1998;Cremer and Cremer, 2001;Shiels et al, 2001;Kozubek et al, 2002;Tanabe et al, 2002). Our approach employs first-order nearest-neighbor statistics, commonly used in ecological studies (Clark and Evans, 1954;Sinclair, 1985), to characterize the spatial randomness of nuclear microenvironments (Fig.…”

Section: Resultsmentioning

confidence: 99%

Quantitative signature for architectural organization of regulatory factors using intranuclear informatics

Young

Zaidi

Furcinitti

et al. 2004

Journal of Cell Science

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Cell culture and transfections ROS 17/2.8 osteosarcoma cells were maintained in F12 with penicillin 4889Regulatory machinery for replication and gene expression is punctately organized in supramolecular complexes that are compartmentalized in nuclear microenvironments. Quantitative approaches are required to understand the assembly of regulatory machinery within the context of nuclear architecture and to provide a mechanistic link with biological control. We have developed 'intranuclear informatics' to quantify functionally relevant parameters of spatially organized nuclear domains. Using this informatics strategy we have characterized post-mitotic reestablishment of focal subnuclear organization of Runx (AML/Cbfa) transcription factors in progeny cells.By analyzing point mutations that abrogate fidelity of Runx intranuclear targeting, we establish molecular determinants for the spatial order of Runx domains. Our novel approach provides evidence that architectural organization of Runx factors may be fundamental to their tissue-specific regulatory function.Supplementary material available online at

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Randomness of spatial distributions of two proteins in the cell nucleus involved in mRNA synthesis and their relationship

Cited by 11 publications

References 21 publications

Statistical Analysis of 3D Images Detects Regular Spatial Distributions of Centromeres and Chromocenters in Animal and Plant Nuclei

Statistical Analysis of 3D Images Detects Regular Spatial Distributions of Centromeres and Chromocenters in Animal and Plant Nuclei

Direct Visualization of a Protein Nuclear Architecture

Quantitative signature for architectural organization of regulatory factors using intranuclear informatics

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