Packaging of the eukaryotic genome into higher order chromatin structures is tightly related to g... more Packaging of the eukaryotic genome into higher order chromatin structures is tightly related to gene expression. Pericentromeric heterochromatin is typified by accumulations of heterochromatin protein 1 (HP1), methylation of histone H3 at lysine 9 (MeH3K9) and global histone deacetylation. HP1 interacts with chromatin by binding to MeH3K9 through the chromodomain (CD). HP1 dimerizes with itself and binds a variety of proteins through its chromoshadow domain. We have analyzed at the single cell level whether HP1 lacking its functional CD is able to induce heterochromatinization in vivo. We used a lac-operator array-based system in mammalian cells to target EGFP-lac repressor tagged truncated HP1α and HP1β to a lac operator containing gene-amplified chromosome region in living cells. After targeting truncated HP1α or HP1β we observe enhanced tri-MeH3K9 and recruitment of endogenous HP1α and HP1β to the chromosome region. We show that CD-less HP1α can induce chromatin condensation, whereas the effect of truncated HP1β is less pronounced. Our results demonstrate that after lac repressor-mediated targeting, HP1α and HP1β without a functional CD are able to induce heterochromatinization.
Proceedings of The National Academy of Sciences, 2009
Genome function in higher eukaryotes involves major changes in the spatial organization of the ch... more Genome function in higher eukaryotes involves major changes in the spatial organization of the chromatin fiber. Nevertheless, our understanding of chromatin folding is remarkably limited. Polymer models have been used to describe chromatin folding. However, none of the proposed models gives a satisfactory explanation of experimental data. In particularly, they ignore that each chromosome occupies a confined space, i.e., the chromosome territory. Here, we present a polymer model that is able to describe key properties of chromatin over length scales ranging from 0.5 to 75 Mb. This random loop (RL) model assumes a self-avoiding random walk folding of the polymer backbone and defines a probability P for 2 monomers to interact, creating loops of a broad size range. Model predictions are compared with systematic measurements of chromatin folding of the q-arms of chromosomes 1 and 11. The RL model can explain our observed data and suggests that on the tens-of-megabases length scale P is small, i.e., 10 -30 loops per 100 Mb. This is sufficient to enforce folding inside the confined space of a chromosome territory. On the 0.5-to 3-Mb length scale chromatin compaction differs in different subchromosomal domains. This aspect of chromatin structure is incorporated in the RL model by introducing heterogeneity along the fiber contour length due to different local looping probabilities. The RL model creates a quantitative and predictive framework for the identification of nuclear components that are responsible for chromatin-chromatin interactions and determine the 3-dimensional organization of the chromatin fiber. genome organization ͉ polymer model ͉ chromatin folding Author contributions: J.M.-L., E.M.M.M., P.J
Three-dimensional (3D) chromatin structure is closely related to genome function, in particular t... more Three-dimensional (3D) chromatin structure is closely related to genome function, in particular transcription. However, the folding path of the chromatin fiber in the interphase nucleus is unknown. Here, we systematically measured the 3D physical distance between pairwise labeled genomic positions in gene-dense, highly transcribed domains and gene-poor less active areas on chromosomes 1 and 11 in G1 nuclei of human primary fibroblasts, using fluorescence in situ hybridization. Interpretation of our results and those published by others, based on polymer physics, shows that the folding of the chromatin fiber can be described as a polymer in a globular state (GS), maintained by intra-polymer attractive interactions that counteract self-avoidance forces. The GS polymer model is able to describe chromatin folding in as well the highly expressed domains as the lowly expressed ones, indicating that they differ in Kuhn length and chromatin compaction. Each type of genomic domain constitutes an ensemble of relatively compact globular folding states, resulting in a considerable cellto- cell variation between otherwise identical cells. We present evidence for different polymer folding regimes of the chromatin fiber on the length scale of a few mega base pairs and on that of complete chromosome arms (several tens of Mb). Our results present a novel view on the folding of the chromatin fiber in interphase and open the possibility to explore the nature of the intra-chromatin fiber interactions.
User interfaces and visualisations are part of group problem solving. Technology is already a par... more User interfaces and visualisations are part of group problem solving. Technology is already a part of daily decision-making in multidisplay environments, both as communication tools and information devices. As these devices, such as large displays and visualisation tools become more accessible, there is an increasing opportunity to develop applications that enhance group decision-making abilities, rather than restrict them. This chapter presents the results of the empirical user study on the effect of the Highlighting-on-Demand concept on situational awareness and satisfaction with the group decision-making process in a real multidisplay environment. Highlighting-on-Demand interface enables a team member who is currently controlling the shared large display to draw attention of the other team members by highlighting certain visualisation. Displaying all alternatives on a shared large display fosters information sharing and the Highlighting-on-Demand interface enables group members to draw attention to certain visualisation, while keeping the other alternatives still in view. The results suggest that when group members use the Highlighting-on-Demand interface during the discussion, the satisfaction with the final group decision increases. Participants expressed willingness to use the Highlighting awareness support for visualising real data (e.g., biomedical, omics experiments) and manipulating how the data is visualised to discuss the experiment results with other team members in real project discussions.
In this paper the motivation, design and application of a distributed blackboard architecture for... more In this paper the motivation, design and application of a distributed blackboard architecture for interactive data visualization is discussed. The main advantages of the architecture are twofold. First, it allows visualization tools to be tightly integrated with simulations. Second, it allows qualitative and quantitative analysis to be combined during the visualization process.
Spot noise and line integral convolution (LIC) are two texture synthesis techniques for vector fi... more Spot noise and line integral convolution (LIC) are two texture synthesis techniques for vector field visualization. The two techniques are compared. Continuous directional convolution is used as a common basis for comparing the techniques. It is shown that the techniques are based on the same mathematical concept. Comparisons of the visual appearance of the output and performance of the algorithms are made.
The design and implementation of an interactive spot noise algorithm is presented. Spot noise is ... more The design and implementation of an interactive spot noise algorithm is presented. Spot noise is a technique which utilizes texture for the visualization of flow fields. Various design tradeoffs are discussed that allow an optimal implementation on a range of high end graphical workstations.
In this case study we discuss an interactive feature tracking system and its use for the analysis... more In this case study we discuss an interactive feature tracking system and its use for the analysis of chromatin decondensation. Features are described as points in a multidimensional attribute space. Distances between points are used as a measure for feature correspondence. Users can interactively experiment with the correspondence measure in order to gain insight in chromatin movement. In addition, by defining time as an attribute, tracking problems related to noisy confocal data can be circumvented.
The design and implementation of an interactive spot noise algorithm is presented. Spot noise is ... more The design and implementation of an interactive spot noise algorithm is presented. Spot noise is a technique which utilizes texture for the visualization of flow fields. Various design tradeoffs are discussed that allow an optimal implementation on a range of high end graphical workstations.
This paper describes BM3D: a method for the analysis of motion in time dependent volume data. Fro... more This paper describes BM3D: a method for the analysis of motion in time dependent volume data. From a sequence of volume data sets a sequence of vector data sets representing the movement of the data is computed. A block matching technique is used for the reconstruction of data movement. The derived vector field can be used for the visualization of time dependent volume data. The method is illustrated in two applications.
Packaging of the eukaryotic genome into higher order chromatin structures is tightly related to g... more Packaging of the eukaryotic genome into higher order chromatin structures is tightly related to gene expression. Pericentromeric heterochromatin is typified by accumulations of heterochromatin protein 1 (HP1), methylation of histone H3 at lysine 9 (MeH3K9) and global histone deacetylation. HP1 interacts with chromatin by binding to MeH3K9 through the chromodomain (CD). HP1 dimerizes with itself and binds a variety of proteins through its chromoshadow domain. We have analyzed at the single cell level whether HP1 lacking its functional CD is able to induce heterochromatinization in vivo. We used a lac-operator array-based system in mammalian cells to target EGFP-lac repressor tagged truncated HP1α and HP1β to a lac operator containing gene-amplified chromosome region in living cells. After targeting truncated HP1α or HP1β we observe enhanced tri-MeH3K9 and recruitment of endogenous HP1α and HP1β to the chromosome region. We show that CD-less HP1α can induce chromatin condensation, whereas the effect of truncated HP1β is less pronounced. Our results demonstrate that after lac repressor-mediated targeting, HP1α and HP1β without a functional CD are able to induce heterochromatinization.
Proceedings of The National Academy of Sciences, 2009
Genome function in higher eukaryotes involves major changes in the spatial organization of the ch... more Genome function in higher eukaryotes involves major changes in the spatial organization of the chromatin fiber. Nevertheless, our understanding of chromatin folding is remarkably limited. Polymer models have been used to describe chromatin folding. However, none of the proposed models gives a satisfactory explanation of experimental data. In particularly, they ignore that each chromosome occupies a confined space, i.e., the chromosome territory. Here, we present a polymer model that is able to describe key properties of chromatin over length scales ranging from 0.5 to 75 Mb. This random loop (RL) model assumes a self-avoiding random walk folding of the polymer backbone and defines a probability P for 2 monomers to interact, creating loops of a broad size range. Model predictions are compared with systematic measurements of chromatin folding of the q-arms of chromosomes 1 and 11. The RL model can explain our observed data and suggests that on the tens-of-megabases length scale P is small, i.e., 10 -30 loops per 100 Mb. This is sufficient to enforce folding inside the confined space of a chromosome territory. On the 0.5-to 3-Mb length scale chromatin compaction differs in different subchromosomal domains. This aspect of chromatin structure is incorporated in the RL model by introducing heterogeneity along the fiber contour length due to different local looping probabilities. The RL model creates a quantitative and predictive framework for the identification of nuclear components that are responsible for chromatin-chromatin interactions and determine the 3-dimensional organization of the chromatin fiber. genome organization ͉ polymer model ͉ chromatin folding Author contributions: J.M.-L., E.M.M.M., P.J
Three-dimensional (3D) chromatin structure is closely related to genome function, in particular t... more Three-dimensional (3D) chromatin structure is closely related to genome function, in particular transcription. However, the folding path of the chromatin fiber in the interphase nucleus is unknown. Here, we systematically measured the 3D physical distance between pairwise labeled genomic positions in gene-dense, highly transcribed domains and gene-poor less active areas on chromosomes 1 and 11 in G1 nuclei of human primary fibroblasts, using fluorescence in situ hybridization. Interpretation of our results and those published by others, based on polymer physics, shows that the folding of the chromatin fiber can be described as a polymer in a globular state (GS), maintained by intra-polymer attractive interactions that counteract self-avoidance forces. The GS polymer model is able to describe chromatin folding in as well the highly expressed domains as the lowly expressed ones, indicating that they differ in Kuhn length and chromatin compaction. Each type of genomic domain constitutes an ensemble of relatively compact globular folding states, resulting in a considerable cellto- cell variation between otherwise identical cells. We present evidence for different polymer folding regimes of the chromatin fiber on the length scale of a few mega base pairs and on that of complete chromosome arms (several tens of Mb). Our results present a novel view on the folding of the chromatin fiber in interphase and open the possibility to explore the nature of the intra-chromatin fiber interactions.
User interfaces and visualisations are part of group problem solving. Technology is already a par... more User interfaces and visualisations are part of group problem solving. Technology is already a part of daily decision-making in multidisplay environments, both as communication tools and information devices. As these devices, such as large displays and visualisation tools become more accessible, there is an increasing opportunity to develop applications that enhance group decision-making abilities, rather than restrict them. This chapter presents the results of the empirical user study on the effect of the Highlighting-on-Demand concept on situational awareness and satisfaction with the group decision-making process in a real multidisplay environment. Highlighting-on-Demand interface enables a team member who is currently controlling the shared large display to draw attention of the other team members by highlighting certain visualisation. Displaying all alternatives on a shared large display fosters information sharing and the Highlighting-on-Demand interface enables group members to draw attention to certain visualisation, while keeping the other alternatives still in view. The results suggest that when group members use the Highlighting-on-Demand interface during the discussion, the satisfaction with the final group decision increases. Participants expressed willingness to use the Highlighting awareness support for visualising real data (e.g., biomedical, omics experiments) and manipulating how the data is visualised to discuss the experiment results with other team members in real project discussions.
In this paper the motivation, design and application of a distributed blackboard architecture for... more In this paper the motivation, design and application of a distributed blackboard architecture for interactive data visualization is discussed. The main advantages of the architecture are twofold. First, it allows visualization tools to be tightly integrated with simulations. Second, it allows qualitative and quantitative analysis to be combined during the visualization process.
Spot noise and line integral convolution (LIC) are two texture synthesis techniques for vector fi... more Spot noise and line integral convolution (LIC) are two texture synthesis techniques for vector field visualization. The two techniques are compared. Continuous directional convolution is used as a common basis for comparing the techniques. It is shown that the techniques are based on the same mathematical concept. Comparisons of the visual appearance of the output and performance of the algorithms are made.
The design and implementation of an interactive spot noise algorithm is presented. Spot noise is ... more The design and implementation of an interactive spot noise algorithm is presented. Spot noise is a technique which utilizes texture for the visualization of flow fields. Various design tradeoffs are discussed that allow an optimal implementation on a range of high end graphical workstations.
In this case study we discuss an interactive feature tracking system and its use for the analysis... more In this case study we discuss an interactive feature tracking system and its use for the analysis of chromatin decondensation. Features are described as points in a multidimensional attribute space. Distances between points are used as a measure for feature correspondence. Users can interactively experiment with the correspondence measure in order to gain insight in chromatin movement. In addition, by defining time as an attribute, tracking problems related to noisy confocal data can be circumvented.
The design and implementation of an interactive spot noise algorithm is presented. Spot noise is ... more The design and implementation of an interactive spot noise algorithm is presented. Spot noise is a technique which utilizes texture for the visualization of flow fields. Various design tradeoffs are discussed that allow an optimal implementation on a range of high end graphical workstations.
This paper describes BM3D: a method for the analysis of motion in time dependent volume data. Fro... more This paper describes BM3D: a method for the analysis of motion in time dependent volume data. From a sequence of volume data sets a sequence of vector data sets representing the movement of the data is computed. A block matching technique is used for the reconstruction of data movement. The derived vector field can be used for the visualization of time dependent volume data. The method is illustrated in two applications.
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Papers by Wim de Leeuw