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  • 1
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    Analysis of combinatorial cis-regulation in synthetic and genomic promoters (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-11-26
    Description: Transcription factor binding sites are being discovered at a rapid pace. It is now necessary to turn attention towards understanding how these sites work in combination to influence gene expression. Quantitative models that accurately predict gene expression from promoter sequence will be a crucial part of solving this problem. Here we present such a model, based on the analysis of synthetic promoter libraries in yeast (Saccharomyces cerevisiae). Thermodynamic models based only on the equilibrium binding of transcription factors to DNA and to each other captured a large fraction of the variation in expression in every library. Thermodynamic analysis of these libraries uncovered several phenomena in our system, including cooperativity and the effects of weak binding sites. When applied to the S. cerevisiae genome, a model of repression by Mig1 (which was trained on synthetic promoters) predicts a number of Mig1-regulated genes that lack significant Mig1-binding sites in their promoters. The success of the thermodynamic approach suggests that the information encoded by combinations of cis-regulatory sites is interpreted primarily through simple protein-DNA and protein-protein interactions, with complicated biochemical reactions-such as nucleosome modifications-being downstream events. Quantitative analyses of synthetic promoter libraries will be an important tool in unravelling the rules underlying combinatorial cis-regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677908/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677908/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gertz, Jason -- Siggia, Eric D -- Cohen, Barak A -- R01 GM078222/GM/NIGMS NIH HHS/ -- R01 GM078222-01A1/GM/NIGMS NIH HHS/ -- R01 GM078222-02/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jan 8;457(7226):215-8. doi: 10.1038/nature07521. Epub 2008 Nov 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genome Sciences, Department of Genetics, Washington University in Saint Louis School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19029883" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Site ; DNA/genetics/metabolism ; DNA-Binding Proteins/metabolism ; Down-Regulation ; *Gene Expression Regulation, Fungal ; *Gene Library ; Genes, Synthetic/*genetics ; Genome, Fungal/*genetics ; Models, Genetic ; Promoter Regions, Genetic/*genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Repressor Proteins/metabolism ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Thermodynamics ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    A nebular origin for chondritic fine-grained phyllosilicates (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-01-25
    Description: Hydrated minerals occur in accretionary rims around chondrules in CM chondrites. Previous models suggested that these phyllosilicates did not form by gas-solid reactions in the canonical solar nebula. We propose that chondrule-forming shock waves in icy regions of the nebula produced conditions that allowed rapid mineral hydration. The time scales for phyllosilicate formation are similar to the time it takes for a shocked system to cool from the temperature of phyllosilicate stability to that of water ice condensation. This scenario allows for simultaneous formation of chondrules and their fine-grained accretionary rims.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciesla, Fred J -- Lauretta, Dante S -- Cohen, Barbara A -- Hood, Lon L -- New York, N.Y. -- Science. 2003 Jan 24;299(5606):549-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Planetary Sciences, Lunar and Planetary Laboratory, University of Arizona, 1629 East University Boulevard, Tucson, AZ 85721, USA. fciesla@lpl.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12543970" target="_blank"〉PubMed〈/a〉
    Keywords: Ice ; *Meteoroids ; Pressure ; *Silicates ; Temperature ; Thermodynamics ; *Water
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Finding functional features in Saccharomyces genomes by phylogenetic footprinting (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-05-31
    Description: The sifting and winnowing of DNA sequence that occur during evolution cause nonfunctional sequences to diverge, leaving phylogenetic footprints of functional sequence elements in comparisons of genome sequences. We searched for such footprints among the genome sequences of six Saccharomyces species and identified potentially functional sequences. Comparison of these sequences allowed us to revise the catalog of yeast genes and identify sequence motifs that may be targets of transcriptional regulatory proteins. Some of these conserved sequence motifs reside upstream of genes with similar functional annotations or similar expression patterns or those bound by the same transcription factor and are thus good candidates for functional regulatory sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cliften, Paul -- Sudarsanam, Priya -- Desikan, Ashwin -- Fulton, Lucinda -- Fulton, Bob -- Majors, John -- Waterston, Robert -- Cohen, Barak A -- Johnston, Mark -- R01 GM63803/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 4;301(5629):71-6. Epub 2003 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12775844" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Base Sequence ; Binding Sites ; Computational Biology ; *Conserved Sequence ; *DNA, Intergenic ; Gene Expression Profiling ; Genes, Fungal ; *Genome, Fungal ; Molecular Sequence Data ; *Phylogeny ; *Regulatory Sequences, Nucleic Acid ; Saccharomyces/classification/*genetics/physiology ; Saccharomyces cerevisiae/genetics/physiology ; Sequence Alignment ; Sequence Analysis, DNA ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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