4,940 research outputs found

    Challenges in experimental data integration within genome-scale metabolic models

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    A report of the meeting "Challenges in experimental data integration within genome-scale metabolic models", Institut Henri Poincar\'e, Paris, October 10-11 2009, organized by the CNRS-MPG joint program in Systems Biology.Comment: 5 page

    Evolution of gene regulation of pluripotency - the case for wiki tracks at genome browsers

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    <p>Abstract</p> <p>Background</p> <p>Experimentally validated data on gene regulation are hard to obtain. In particular, information about transcription factor binding sites in regulatory regions are scattered around in the literature. This impedes their systematic in-context analysis, e.g. the inference of their conservation in evolutionary history.</p> <p>Results</p> <p>We demonstrate the power of integrative bioinformatics by including curated transcription factor binding site information into the UCSC genome browser, using wiki and custom tracks, which enable easy publication of annotation data. Data integration allows to investigate the evolution of gene regulation of the pluripotency-associated genes Oct4, Sox2 and Nanog. For the first time, experimentally validated transcription factor binding sites in the regulatory regions of all three genes were assembled together based on manual curation of data from 39 publications. Using the UCSC genome browser, these data were then visualized in the context of multi-species conservation based on genomic alignment. We confirm previous hypotheses regarding the evolutionary age of specific regulatory patterns, establishing their "deep homology". We also confirm some other principles of Carroll's "Genetic theory of Morphological Evolution", such as "mosaic pleiotropy", exemplified by the dual role of Sox2 reflected in its regulatory region.</p> <p>Conclusions</p> <p>We were able to elucidate some aspects of the evolution of gene regulation for three genes associated with pluripotency. Based on the expected return on investment for the community, we encourage other scientists to contribute experimental data on gene regulation (original work as well as data collected for reviews) to the UCSC system, to enable studies of the evolution of gene regulation on a large scale, and to report their findings.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Gustavo Glusman and Dr. Juan Caballero, Institute for Systems Biology, Seattle, USA (nominated by Dr. Doron Lancet, Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel), Dr. Niels Grabe, TIGA Center (BIOQUANT) and Medical Systems Biology Group, Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Germany (nominated by Dr. Mikhail Gelfand, Department of Bioinformatics, Institute of Information Transfer Problems, Russian Academy of Science, Moscow, Russian Federation) and Dr. Franz-Josef MĂŒller, Center for Regenerative Medicine, The Scripps Research Institute, La Jolla, CA, USA and University Hospital for Psychiatry and Psychotherapy (part of ZIP gGmbH), University of Kiel, Germany (nominated by Dr. Trey Ideker, University of California, San Diego, La Jolla CA, United States).</p

    Recent advances in computational epigenetics

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    The developmental expression dynamics of Drosophila melanogaster transcription factors.

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    BACKGROUND: Site-specific transcription factors (TFs) are coordinators of developmental and physiological gene expression programs. Their binding to cis-regulatory modules of target genes mediates the precise cell- and context-specific activation and repression of genes. The expression of TFs should therefore reflect the core expression program of each cell. RESULTS: We studied the expression dynamics of about 750 TFs using the available genomics resources in Drosophila melanogaster. We find that 95% of these TFs are expressed at some point during embryonic development, with a peak roughly between 10 and 12 hours after egg laying, the core stages of organogenesis. We address the differential utilization of DNA-binding domains in different developmental programs systematically in a spatio-temporal context, and show that the zinc finger class of TFs is predominantly early expressed, while Homeobox TFs exhibit later expression in embryogenesis. CONCLUSIONS: Previous work, dissecting cis-regulatory modules during Drosophila development, suggests that TFs are deployed in groups acting in a cooperative manner. In contrast, we find that there is rapid exchange of co-expressed partners amongst the fly TFs, at rates similar to the genome-wide dynamics of co-expression clusters. This suggests there may also be a high level of combinatorial complexity of TFs at cis-regulatory modules.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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