Physical properties of naked DNA influence nucleosome positioning and correlate with transcription start and termination sites in yeast

Abstract Background In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive. Results Naked (histone-free) and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase) and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions. Conclusions Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site) and TTS (Transcription Termination Site) (at least in yeast) is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression

Is Design Really Social

There are many who will readily agree with Mitchell's assertion that “the most interesting new directions (for computer-aided design) are suggested by the growing convergence of computation and telecommunication. This allows us to treat designing not just as a technical process... but also as a social process.” [Mitchell 1995]. The assumption is that design was a social process until users of computer-aided design systems were distracted into treating it as a merely technical process. Most readers will assume that this convergence must and will lead to increased communication between design participants, that better social interaction leads to be better design. The unspoken assumption appears to be that putting the participants into an environment with maximal communication channels will result in design collaboration. The tools provided, therefore, must permit the best communication and the best social interaction. We see a danger here, a pattern being repeated which may lead us into less than useful activities. As with several (popular) architectural design or modelling systems already available, however, computer system implementations all too often are poor imitations manual systems. For example, few in the field will argue with the statement that the storage of data in layers in a computer-aided drafting system is an dispensable approach. Layers derive from manual overlay drafting technology [Stitt 1984] which was regarded as an advanced (manual) production concept at the time many software engineers were specifying CAD software designs. Early implementations of CAD systems (such as RUCAPS, GDS, Computervision) avoided such data organisation, the software engineers recognising that object-based structures are more flexible, permitting greater control of data editing and display. Layer-based systems, however, are easier to implement in software, more familiar to the user and hence easier to explain, initially easier to use but more limiting for an experienced and thoughtful user, leading in the end to a lesser quality in resultant drawings and significant problems in output control (see Richens [1990], pp. 31-40 for a detailed analysis of such features and constraints). Here then we see the design for architectural software faithfully but inappropriately following manual methods. So too is there a danger of assuming that the best social interaction is that done face-to-face, therefore all collaborative design communications environments must mimic face-to-face

Is Design Really Social

There are many who will readily agree with Mitchellis assertion that “the most interesting new directions (for computer-aided design) are suggested by the growing convergence of computation and telecommunication. This allows us to treat designing not just as a technical process... but also as a social process.i [Mitchell 1995]. The assumption is that design was a social process until users of computer-aided design systems were distracted into treating it as a merely technical process. Most readers will assume that this convergence must and will lead to increased communication between design participants, that better social interaction leads to be better design. The unspoken assumption appears to be that putting the participants into an environment with maximal communication channels will result in design collaboration. The tools provided, therefore, must permit the best communication and the best social interaction. We think it essential to examine the foundations and assumptions on which software and environments are designed to support collaborative design communication. Of particular interest to us in this paper is the assumption about the “social” nature of design. Early research in computer-assisted design collaborations has jumped immediately into conclusions about communicative models which lead to high-bandwidth video connections as the preferred channel of collaboration. The unstated assumption is that computer-supported design environments are not adequate until they replicate in full the sensation of being physically present in the same space as the other participants (you are not there until you are really there). It is assumed that the real social process of design must include all the signals used to establish and facilitate face-to-face communication, including gestures, body language and all outputs of drawing (e.g. Tang [1991]). In our specification of systems for virtual design communities, are we about to fall into the same traps as drafting systems did

The First Virtual Environment Design Studio

Since 1993 schools of architecture all over the world conduct in various forms of Virtual Design Studio (VDS). They have become an established part of teaching design within the digital realm. They vary in task and structure, are purely text-based or include various forms of interactive, synchronous or asynchronous collaboration. However, “virtual” always refers to the method of communication and exchange of design and ideas. Students have never designed within immersive virtuality. This paper describes the first successful attempt to conduct a Joint Design Studio, which uses Virtual Environment (VE) as tool of design and communication between the remote partners. This first VeDS focused on how architectural students make use of this particular different approach to design within immersive three-dimensional VEs. For example, the students created 3D-immersive design proposals, explored dependencies to textual description of initial intentions and communicated between local and remote team-partners in immersive VE as well as textbased communication-channels. The paper subsequently describes the VeDS, its set-up, realization and outcome. We discuss frameworks and factors influencing how architectural students communicate their proposals in immersive VeDS, and how this new approach of design studio enables new forms of design expressions