The role of Smarcad1 in retroviral repression in mouse embryonic stem cells.

BACKGROUND: Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood. RESULTS: In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states. CONCLUSIONS: Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.

Differential effect of histone H3.3 depletion on retroviral repression in embryonic stem cells.

BACKGROUND: Integration of retroviruses into the host genome can impair the genomic and epigenomic integrity of the cell. As a defense mechanism, epigenetic modifications on the proviral DNA repress retroviral sequences in mouse embryonic stem cells (ESC). Here, we focus on the histone 3 variant H3.3, which is abundant in active transcription zones, as well as centromeres and heterochromatinized repeat elements, e.g., endogenous retroviruses (ERV). RESULTS: To understand the involvement of H3.3 in the epigenetic silencing of retroviral sequences in ESC, we depleted the H3.3 genes in ESC and transduced the cells with GFP-labeled MLV pseudovirus. This led to altered retroviral repression and reduced Trim28 recruitment, which consequently led to a loss of heterochromatinization in proviral sequences. Interestingly, we show that H3.3 depletion has a differential effect depending on which of the two genes coding for H3.3, H3f3a or H3f3b, are knocked out. Depletion of H3f3a resulted in a transient upregulation of incoming retroviral expression and ERVs, while the depletion of H3f3b did not have the same effect and repression was maintained. However, the depletion of both genes resulted in a stable activation of the retroviral promoter. These findings suggest that H3.3 is important for regulating retroviral gene expression in mouse ESC and provide evidence for a distinct function of the two H3.3 genes in this regulation. Furthermore, we show that Trim28 is needed for depositing H3.3 in retroviral sequences, suggesting a functional interaction between Trim28 recruitment and H3.3 loading. CONCLUSIONS: Identifying the molecular mechanisms by which H3.3 and Trim28 interact and regulate retroviral gene expression could provide a deeper understanding of the fundamental processes involved in retroviral silencing and the general regulation of gene expression, thus providing new answers to a central question of stem cell biology.

Trim24 and Trim33 Play a Role in Epigenetic Silencing of Retroviruses in Embryonic Stem Cells.

Embryonic stem cells (ESC) have the ability to epigenetically silence endogenous and exogenous retroviral sequences. Trim28 plays an important role in establishing this silencing, but less is known about the role other Trim proteins play. The Tif1 family is a sub-group of the Trim family, which possess histone binding ability in addition to the distinctive RING domain. Here, we have examined the interaction between three Tif1 family members, namely Trim24, Trim28 and Trim33, and their function in retroviral silencing. We identify a complex formed in ESC, comprised of these three proteins. We further show that when Trim33 is depleted, the complex collapses and silencing efficiency of both endogenous and exogenous sequences is reduced. Similar transcriptional activation takes place when Trim24 is depleted. Analysis of the H3K9me3 chromatin modification showed a decrease in this repressive mark, following both Trim24 and Trim33 depletion. As Trim28 is an identified binding partner of the H3K9 methyltransferase ESET, this further supports the involvement of Trim28 in the complex. The results presented here suggest that a complex of Tif1 family members, each of which possesses different specificity and efficiency, contributes to the silencing of retroviral sequences in ESC.

Surface Regions of Interest for Viewpoint Selection.

While the detection of the interesting regions in images has been extensively studied, relatively few papers have addressed surfaces. This paper proposes an algorithm for detecting the regions of interest of surfaces. It looks for regions that are distinct both locally and globally and accounts for the distance to the foci of attention. It is also shown how this algorithm can be adopted to saliency detection in point clouds. Many applications can utilize these regions. In this paper we explore one such application-viewpoint selection. The most informative views are those that collectively provide the most descriptive presentation of the surface. We show that our results compete favorably with the state-of-the-art results.

Animation of flocks flying in line formations.

We provide a biologically motivated technique for modeling and animating bird flocks in flight, which produces plausible and realistic-looking flock animations. While most previous approaches have focused on animating cluster formations, this article introduces a technique for animating flocks that fly in certain patterns, so-called line formations. We distinguish between the behavior of such flocks during initiation and their behavior during steady flight. Our simulation of the initiation stage is rule-based and incorporates an artificial bird model. Our simulation of the steady-flight stage combines a data-driven approach and an energy-savings model.

Context-aware saliency detection.

We propose a new type of saliency­context-aware saliency­which aims at detecting the image regions that represent the scene. This definition differs from previous definitions whose goal is to either identify fixation points or detect the dominant object. In accordance with our saliency definition, we present a detection algorithm which is based on four principles observed in the psychological literature. The benefits of the proposed approach are evaluated in two applications where the context of the dominant objects is just as essential as the objects themselves. In image retargeting, we demonstrate that using our saliency prevents distortions in the important regions. In summarization, we show that our saliency helps to produce compact, appealing, and informative summaries.

Uncluttering graph layouts using anisotropic diffusion and mass transport.

Many graph layouts include very dense areas, making the layout difficult to understand. In this paper, we propose a technique for modifying an existing layout in order to reduce the clutter in dense areas. A physically inspired evolution process based on a modified heat equation is used to create an improved layout density image, making better use of available screen space. Using results from optimal mass transport problems, a warp to the improved density image is computed. The graph nodes are displaced according to the warp. The warp maintains the overall structure of the graph, thus limiting disturbances to the mental map, while reducing the clutter in dense areas of the layout. The complexity of the algorithm depends mainly on the resolution of the image visualizing the graph and is linear in the size of the graph. This allows scaling the computation according to required running times. It is demonstrated how the algorithm can be significantly accelerated using a graphics processing unit (GPU), resulting in the ability to handle large graphs in a matter of seconds. Results on several layout algorithms and applications are demonstrated.

Online dynamic graph drawing.

This paper presents an algorithm for drawing a sequence of graphs online. The algorithm strives to maintain the global structure of the graph and thus the user's mental map, while allowing arbitrary modifications between consecutive layouts. The algorithm works online and uses various execution culling methods in order to reduce the layout time and handle large dynamic graphs. Techniques for representing graphs on the GPU allow a speedup by a factor of up to 17 compared to the CPU implementation. The scalability of the algorithm across GPU generations is demonstrated. Applications of the algorithm to the visualization of discussion threads in Internet sites and to the visualization of social networks are provided.

Multi-level graph layout on the GPU.

This paper presents a new algorithm for force directed graph layout on the GPU. The algorithm, whose goal is to compute layouts accurately and quickly, has two contributions. The first contribution is proposing a general multi-level scheme, which is based on spectral partitioning. The second contribution is computing the layout on the GPU. Since the GPU requires a data parallel programming model, the challenge is devising a mapping of a naturally unstructured graph into a well-partitioned structured one. This is done by computing a balanced partitioning of a general graph. This algorithm provides a general multi-level scheme, which has the potential to be used not only for computation on the GPU, but also on emerging multi-core architectures. The algorithm manages to compute high quality layouts of large graphs in a fraction of the time required by existing algorithms of similar quality. An application for visualization of the topologies of ISP (Internet Service Provider) networks is presented.