Wim C. de Leeuw

The Three-Dimensional Structure of Human Interphase Chromosomes Is Related to the Transcriptome Map

ABSTRACT The three-dimensional (3D) organization of the chromosomal fiber in the human interphase nucleus is an important but poorly understood aspect of gene regulation. Here we quantitatively analyze and compare the 3D structures of two types of genomic domains as defined by the human transcriptome map. While ridges are gene dense and show high expression levels, antiridges, on the other hand, are gene poor and carry genes that are expressed at low levels. We show that ridges are in general less condensed, more irregularly shaped, and located more closely to the nuclear center than antiridges. Six human cell lines that display different gene expression patterns and karyotypes share these structural parameters of chromatin. This shows that the chromatin structures of these two types of genomic domains are largely independent of tissue-specific variations in gene expression and differentiation state. Moreover, we show that there is remarkably little intermingling of chromatin from different parts of the same chromosome in a chromosome territory, neither from adjacent nor from distant parts. This suggests that the chromosomal fiber has a compact structure that sterically suppresses intermingling. Together, our results reveal novel general aspects of 3D chromosome architecture that are related to genome structure and function.

In Vivo HP1 Targeting Causes Large-Scale Chromatin Condensation and Enhanced Histone Lysine Methylation

ABSTRACT Changes in chromatin structure are a key aspect in the epigenetic regulation of gene expression. We have used a lac operator array system to visualize by light microscopy the effect of heterochromatin protein 1 (HP1) α (HP1α) and HP1β on large-scale chromatin structure in living mammalian cells. The structure of HP1, containing a chromodomain, a chromoshadow domain, and a hinge domain, allows it to bind to a variety of proteins. In vivo targeting of an enhanced green fluorescent protein-tagged HP1-lac repressor fusion to a lac operator-containing, gene-amplified chromosome region causes local condensation of the higher-order chromatin structure, recruitment of the histone methyltransferase SETDB1, and enhanced trimethylation of histone H3 lysine 9. Polycomb group proteins of both the HPC/HPH and the EED/EZH2 complexes, which are involved in the heritable repression of gene activity, are not recruited to the amplified chromosome region by HP1α and HP1β in vivo targeting. HP1α targeting causes the recruitment of endogenous HP1β to the chromatin region and vice versa, indicating a direct interaction between the two HP1 homologous proteins. Our findings indicate that HP1α and HP1β targeting is sufficient to induce heterochromatin formation.

Visualization of Global Flow Structures Using Multiple Levels of Topology

The technique for visualizing topological information in fluid flows is well known. However, when the technique is used in complex and information rich data sets, the result will be a cluttered image which is difficult to interpet. This paper presents a technique for the visualization of multi-level topology in flow data sets. It provides the user with a mechanism to visualize the topology without excessive cluttering while maintaining the global structure of the flow.

Divide and Conquer Spot Noise

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.Two applications are given: the steering of a smog prediction simulation and browsing a very large data set resulting from a direct numerical simulation of turbulence. These applications provide the motivation for the need of interactive visualization techniques.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.Two applications are given: the steering of a smog prediction simulation and browsing a very large data set resulting from a direct numerical simulation of turbulence. These applications provide the motivation for the need of interactive visualization techniques.

Multi-level topology for flow visualization

Abstract The technique for visualizing topological information in fluid flows is well known. However, when the technique is used in complex and information-rich data sets, the result will be a cluttered image which is difficult to interpret. This paper presents a technique for the visualization of multi-level topology in flow data sets. It provides the user with a mechanism to visualize the topology without excessive cluttering while maintaining the global structure of the flow.

Truncated HP1 lacking a functional chromodomain induces heterochromatinization upon in vivo targeting

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.

Exploration of large image collections using virtual reality devices

An image browser for the exploration of image collections is described The approach taken is to utilize VR input devices to develop more intuitive interaction metaphors that allow users to navigate through large collections of images. The browser presents query results as a strip of images and interaction with the strip is realized by interpreting the users head movements. The browser is used as a front end to a visual information retrieval system.

Visualization of Multi Dimensional Data Using Structure Preserving Projection Methods

Multi Dimensional Scaling is a structure preserving projection method that allows for the visualization of multidimensional data. In this paper we discuss our practical experience in using MDS as a projection method in three different application scenarios. Various reasons are given why structure preserving proxad jection methods are useful for the analysis of multidimensional data. We discuss two visual forms (glyphs, heightfields) which can be used to represent the output of the projection methods. In this paper we discuss our practical experience in using Multi Dimensional Scaling (MDS) for the visualization of multidimensional data. We show how MDS is used to gain insight into multidimensional spaces that are represented in a table. A large class of data can be characterized by tables. Such tables can be described by a matrix of attribute variables in one dimension and the outcome of specific cases in the other. Discovery and understanding of the structure in this type of data has many applications in science and business, [1]. Here the word structure refers to geometric relationships among subsets of the data variables in the table. Examples of structure include clusters, regular patterns, outliers, distance relations, proximity of data points etc. There are many numerical and statistical techniques that can be used to anxad alyze structural information from multidimensional data tables. These techxad niques can be used to automatically extract certain structural properties from the data. Examples of such techniques are principal component analysis (peA),