200 research outputs found

    A framework to identify epigenome and transcription factor crosstalk

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    While changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. To systematically identify transcription factors (TFs) that can direct chromatin changes during cell fate decisions, we model the genome-wide dynamics of chromatin marks in terms of computationally predicted TF binding sites. By applying this computational approach to a time course of Polycomb-mediated H3K27me3 marks during neuronal differentiation of murine stem cells, we identify several motifs that likely regulate dynamics of this chromatin mark. Among these, the motifs bound by REST and by the SNAIL family of TFs are predicted to transiently recruit H3K27me3 in neuronal progenitors. We validate these predictions experimentally and show that absence of REST indeed causes loss of H3K27me3 at target promoters in trans, specifically at the neuronal progenitor state. Moreover, using targeted transgenic insertion, we show that promoter fragments containing REST or SNAIL binding sites are sufficient to recruit H3K27me3 in cis, while deletion of these sites results in loss of H3K27me3. These findings illustrate that the occurrence of TF binding sites can determine chromatin dynamics. Local determination of Polycomb activity by Rest and Snail motifs exemplifies such TF based regulation of chromatin. Furthermore, our results show that key TFs can be identified ab initio through computational modeling of epigenome datasets using a modeling approach that we make readily accessible

    Advanced Mirror Technology Development (AMTD) Thermal Trade Studies

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    Advanced Mirror Technology Development (AMTD) is being done at Marshall Space Flight Center (MSFC) in preparation for the next Ultraviolet, Optical, Infrared (UVOIR) space observatory. A likely science mission of that observatory is the detection and characterization of 'Earth-like' exoplanets. Direct exoplanet observation requires a telescope to see a planet that is 10-10 times dimmer than its host star. To accomplish this using an internal coronagraph requires a telescope with an ultra-stable wavefront. This paper investigates two topics: 1) parametric relationships between a primary mirror's thermal parameters and wavefront stability, and 2) optimal temperature profiles in the telescope's shroud and heater plate that minimize static wavefront error (WFE) in the primary mirror

    MotEvo: integrated Bayesian probabilistic methods for inferring regulatory sites and motifs on multiple alignments of DNA sequences

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    Motivation: Probabilistic approaches for inferring transcription factor binding sites (TFBSs) and regulatory motifs from DNA sequences have been developed for over two decades. Previous work has shown that prediction accuracy can be significantly improved by incorporating features such as the competition of multiple transcription factors (TFs) for binding to nearby sites, the tendency of TFBSs for co-regulated TFs to cluster and form cis-regulatory modules and explicit evolutionary modeling of conservation of TFBSs across orthologous sequences. However, currently available tools only incorporate some of these features, and significant methodological hurdles hampered their synthesis into a single consistent probabilistic framework. Results: We present MotEvo, a integrated suite of Bayesian probabilistic methods for the prediction of TFBSs and inference of regulatory motifs from multiple alignments of phylogenetically related DNA sequences, which incorporates all features just mentioned. In addition, MotEvo incorporates a novel model for detecting unknown functional elements that are under evolutionary constraint, and a new robust model for treating gain and loss of TFBSs along a phylogeny. Rigorous benchmarking tests on ChIP-seq datasets show that MotEvo's novel features significantly improve the accuracy of TFBS prediction, motif inference and enhancer prediction. Availability: Source code, a user manual and files with several example applications are available at www.swissregulon.unibas.ch. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

    SwissRegulon, a database of genome-wide annotations of regulatory sites: recent updates

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    Identification of genomic regulatory elements is essential for understanding the dynamics of cellular processes. This task has been substantially facilitated by the availability of genome sequences for many species and high-throughput data of transcripts and transcription factor (TF) binding. However, rigorous computational methods are necessary to derive accurate genome-wide annotations of regulatory sites from such data. SwissRegulon (http://swissregulon.unibas.ch) is a database containing genome-wide annotations of regulatory motifs, promoters and TF binding sites (TFBSs) in promoter regions across model organisms. Its binding site predictions were obtained with rigorous Bayesian probabilistic methods that operate on orthologous regions from related genomes, and use explicit evolutionary models to assess the evidence of purifying selection on each site. New in the current version of SwissRegulon is a curated collection of 190 mammalian regulatory motifs associated with ∼340 TFs, and TFBS annotations across a curated set of ∼35 000 promoters in both human and mouse. Predictions of TFBSs for Saccharomyces cerevisiae have also been significantly extended and now cover 158 of yeast's ∼180 TFs. All data are accessible through both an easily navigable genome browser with search functions, and as flat files that can be downloaded for further analysi

    The status of water and sanitation among Pacific Rim nations

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    Analysis of relationships among national wealth, access to improved water supply and sanitation facilities, and population health indices suggests that the adequacy of water resources at the national level is a poor predictor of economic development - namely, that low water stress is neither necessary nor sufficient for economic development at the present state of water stress among Pacific Rim nations. Although nations differ dramatically in terms of priority provided to improved water and sanitation, there is some level of wealth (per capita GNP) at which all nations promote the development of essential environmental services. Among the Pacific Rim countries for which there are data, no nation with a per capita GNP < US18,000peryearhasfailedtoprovidenearuniversalaccesstoimprovedwatersupplyandsanitation.BelowUS18,000 per year has failed to provide near universal access to improved water supply and sanitation. Below US18,000/person-year, however, there are decided differences in the provision of sanitary services (improved water supply and sanitation) among nations with similar economic success. There is a fairly strong relationship between child mortality/life expectancy and access to improved sanitation, as expected from the experiences of developed nations. Here no attempt is made to produce causal relationships among these data. Failure to meet Millennium Development Goals for the extension of improved sanitation is frequently evident in nations with large rural populations. Under those circumstances, capital intensive water and sanitation facilities are infeasible, and process selection for water/wastewater treatment requires an adaptation to local conditions, the use of appropriate materials, etc., constraints that are mostly absent in the developed world. Exceptions to these general ideas exist in water-stressed parts of developed countries, where water supplies are frequently augmented by water harvesting, water reclamation/reuse, and the desalination of brackish water resources. Each of these processes involves public acceptance of water resources that are at least initially of inferior quality. Despite predictions of looming increases in water stress throughout the world, adaptation and resourcefulness generally allow us to meet water demand while pursuing rational economic development, even in the most water-stressed areas of the Pacific Rim

    Field Key to Larvae in Alfalfa

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    The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311.Entomology and Plant Patholog

    Field Key to Beetles in Pines

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    The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311.Entomology and Plant Patholog

    Field Key to Larvae in Peanuts

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    The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311.Entomology and Plant Patholog

    Field Key to Larvae in Soybeans

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    The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311.Entomology and Plant Patholog

    Field Key to Larvae in Pecans

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    The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311.Entomology and Plant Patholog
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