Differential Chromosome Conformations as Hallmarks of Cellular Identity Revealed by Mathematical Polymer Modeling
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{"title"=>"Differential Chromosome Conformations as Hallmarks of Cellular Identity Revealed by Mathematical Polymer Modeling", "type"=>"journal", "authors"=>[{"first_name"=>"Imen", "last_name"=>"Lassadi", "scopus_author_id"=>"35741013000"}, {"first_name"=>"Alain", "last_name"=>"Kamgoué", "scopus_author_id"=>"12800261800"}, {"first_name"=>"Isabelle", "last_name"=>"Goiffon", "scopus_author_id"=>"18436712200"}, {"first_name"=>"Nicolas", "last_name"=>"Tanguy-le-Gac", "scopus_author_id"=>"6507571391"}, {"first_name"=>"Kerstin", "last_name"=>"Bystricky", "scopus_author_id"=>"6602383714"}], "year"=>2015, "source"=>"PLoS Computational Biology", "identifiers"=>{"issn"=>"15537358", "scopus"=>"2-s2.0-84943200871", "pmid"=>"26030148", "doi"=>"10.1371/journal.pcbi.1004306", "pui"=>"607497668", "sgr"=>"84943200871"}, "id"=>"312687b9-5686-3a14-84cb-0e3eae74c131", "abstract"=>"Inherently dynamic, chromosomes adopt many different conformations in response to DNA metabolism. Models of chromosome organization in the yeast nucleus obtained from genome-wide chromosome conformation data or biophysical simulations provide important insights into the average behavior but fail to reveal features from dynamic or transient events that are only visible in a fraction of cells at any given moment. We developed a method to determine chromosome conformation from relative positions of three fluorescently tagged DNA in living cells imaged in 3D. Cell type specific chromosome folding properties could be assigned based on positional combinations between three loci on yeast chromosome 3. We determined that the shorter left arm of chromosome 3 is extended in MATα cells, but can be crumpled in MATa cells. Furthermore, we implemented a new mathematical model that provides for the first time an estimate of the relative physical constraint of three linked loci related to cellular identity. Variations in this estimate allowed us to predict functional consequences from chromatin structural alterations in asf1 and recombination enhancer deletion mutant cells. The computational method is applicable to identify and characterize dynamic chromosome conformations in any cell type.", "link"=>"http://www.mendeley.com/research/differential-chromosome-conformations-hallmarks-cellular-identity-revealed-mathematical-polymer-mode", "reader_count"=>35, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>10, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>10, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>12, "Mathematics"=>1, "Agricultural and Biological Sciences"=>16, "Physics and Astronomy"=>2, "Chemical Engineering"=>1, "Chemistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Mathematics"=>{"Mathematics"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Germany"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2091261"], "description"=>"<p>As in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#pcbi.1004306.g002\" target=\"_blank\">Fig 2B</a>, <i>HML</i>, <i>MAT</i> and <i>HMR</i> were labelled. Examples of density maps (d1 = <i>HML-MAT</i>/θ at <i>MAT</i>) are shown to compare the distribution between the 3 loci in wt and mutant cells. Red arrows highlight changes. An overlay of the contours of the density area representing 30% of the analyzed <i>wt</i> (black) and mutant (red) is represented. The correlation factor c is given for 30% contour. Complete sets of density maps are shown in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#pcbi.1004306.s005\" target=\"_blank\">S5</a> and <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#pcbi.1004306.s007\" target=\"_blank\">S7</a> Figs. A) wt versus <i>asf1</i>. B) wt versus a strain in which the recombination enhancer element (Δre) was deleted.</p>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433164, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004306.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conformation_of_chromosome_3_is_altered_in_asf1_mutant_cells_and_in_the_absence_of_the_recombination_enhancer_element_/1433164", "title"=>"Conformation of chromosome 3 is altered in <i>asf1</i> mutant cells and in the absence of the recombination enhancer element.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-01 04:42:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2091256"], "description"=>"<p>A) 3D data are projected onto a unique 2D plane (eg. d1/θ; 9 projections can be generated from each data set. Density maps (warm colors for high density and cold colors for weak density in 10% increments) are generated for each projection in 2D. Examples shown are density maps where the origin is set to the red spot (R), the d1 distances (vector RB red to blue) are aligned and plotted relative to the angle θ of the RGB triangle at R. left panel: R = <i>HML</i>, d1 = RB = <i>HML</i>—<i>HMR</i>), θ at <i>HML</i>. Center panel: Example of a density map obtained from a simulation based on a random draw of relative positions between 3 loci. Right panel: <i>TelVI</i> = R, <i>ARS</i>1413 = B and <i>MAT</i>. B-C) <i>HML</i>, <i>MAT</i> and <i>HMR</i> (B; YIL30/YIL31; n = 223 and 276)) or <i>LEU</i>, <i>MAT</i> and <i>HML</i> (C; YIL32/33; n = 409 and 323) were labelled using TetO/mRFP-tetR, λO/ λcI-YFP and LacO/CFP-lacI respectively. Examples of density maps are shown to compare the distribution between the 3 loci in <i>MAT</i><b>a</b> and <i>MAT</i>α cells. Red arrows highlight changes between <i>MAT</i><b>a</b> and <i>MAT</i>α cells. An overlay of the contours of the density area representing 30% of the analyzed <i>MAT</i><b>a</b> (black) and <i>MAT</i> α (red) is represented. The correlation factor c is given for 30% contour. Complete sets of density maps are shown in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#pcbi.1004306.s002\" target=\"_blank\">S2</a>–<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#pcbi.1004306.s003\" target=\"_blank\">S3</a> Figs.</p>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433159, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004306.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Folding_of_the_left_arm_of_the_chromosome_3_differs_in_a_subset_of_MAT_a_and_MAT_cells_/1433159", "title"=>"Folding of the left arm of the chromosome 3 differs in a subset of <i>MAT</i>a and <i>MAT</i>α cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-01 04:42:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2091266"], "description"=>"<p>Yeast strains used in this study.</p>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433169, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004306.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Yeast_strains_used_in_this_study_/1433169", "title"=>"Yeast strains used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-01 04:42:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2091264"], "description"=>"<p>Labeled loci are indicated. Not to scale.</p>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433167, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004306.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_representation_of_the_folding_of_chromosome_3_in_MAT_a_and_MAT_cells_only_prominent_features_determined_in_this_study_are_included_/1433167", "title"=>"Schematic representation of the folding of chromosome 3 in <i>MAT</i>a and <i>MAT</i>α cells—only prominent features determined in this study are included.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-01 04:42:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2091278", "https://ndownloader.figshare.com/files/2091279", "https://ndownloader.figshare.com/files/2091280", "https://ndownloader.figshare.com/files/2091281", "https://ndownloader.figshare.com/files/2091282", "https://ndownloader.figshare.com/files/2091283", "https://ndownloader.figshare.com/files/2091284", "https://ndownloader.figshare.com/files/2091285"], "description"=>"<div><p>Inherently dynamic, chromosomes adopt many different conformations in response to DNA metabolism. Models of chromosome organization in the yeast nucleus obtained from genome-wide chromosome conformation data or biophysical simulations provide important insights into the average behavior but fail to reveal features from dynamic or transient events that are only visible in a fraction of cells at any given moment. We developed a method to determine chromosome conformation from relative positions of three fluorescently tagged DNA in living cells imaged in 3D. Cell type specific chromosome folding properties could be assigned based on positional combinations between three loci on yeast chromosome 3. We determined that the shorter left arm of chromosome 3 is extended in <i>MAT</i>α cells, but can be crumpled in <i>MAT</i><b>a</b> cells. Furthermore, we implemented a new mathematical model that provides for the first time an estimate of the relative physical constraint of three linked loci related to cellular identity. Variations in this estimate allowed us to predict functional consequences from chromatin structural alterations in <i>asf1</i> and recombination enhancer deletion mutant cells. The computational method is applicable to identify and characterize dynamic chromosome conformations in any cell type.</p></div>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433181, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1004306.s001", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s002", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s003", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s004", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s005", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s006", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s007", "https://dx.doi.org/10.1371/journal.pcbi.1004306.s008"], "stats"=>{"downloads"=>6, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_Chromosome_Conformations_as_Hallmarks_of_Cellular_Identity_Revealed_by_Mathematical_Polymer_Modeling_/1433181", "title"=>"Differential Chromosome Conformations as Hallmarks of Cellular Identity Revealed by Mathematical Polymer Modeling", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-01 04:42:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2091258"], "description"=>"<p>A) The forward mathematical approach allows determining features of a subpopulation of relative positions between 3 loci in space. The inverse computational approach consists in modeling the relative positions or survival zones of loci whose positions are spatially linked. The underlying polymer fiber imposes constraints on the positions each locus can adapt. Iterative calculation defines the survival zones of each locus (or node) which can predict biological relevant features. B-C) Survival Zones (Z) of <i>HML</i>, <i>MAT</i> and <i>HMR</i>. The initial position of the 3 loci is set based on the estimated conformation for Chr3 (B). Iterations were run using <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#pcbi.1004306.e050\" target=\"_blank\">Eq 25</a> (see <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004306#sec002\" target=\"_blank\">Methods</a>) and the statistically most significant zones are represented for wt, <i>asf1</i> mutants and strains in which the recombination enhancer element was deleted (C).</p>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433162, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004306.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_abstract_model_to_determine_the_relative_physical_constraint_of_three_linked_loci_in_wt_and_mutant_strains_/1433162", "title"=>"An abstract model to determine the relative physical constraint of three linked loci in wt and mutant strains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-01 04:42:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2091252"], "description"=>"<p>A) Representative wide-field fluorescent images of the the mRFP-tetR, λcI-YFP and CFP-lacI foci at <i>HML</i>, <i>MAT and HMR</i>. Insertion sites of the TetO, λO and LacO arrays on S.c. Chr3 are shown. B) Combinations of the geometric coordinates d1, d2, d3 are plotted for each nucleus in <i>MAT</i><b>a</b> (black dots) and <i>MAT</i>α (blue dots). The 50% most frequent combinations in <i>MAT</i><b>a</b> (red) and <i>MAT</i>α (green) are included in a 3D volume.</p>", "links"=>[], "tags"=>["MAT α cells", "Differential Chromosome Conformations", "yeast chromosome 3.", "recombination enhancer deletion", "Mathematical Polymer Modeling", "dna", "conformation", "Cellular Identity Revealed", "cell type"], "article_id"=>1433156, "categories"=>["Biological Sciences"], "users"=>["Imen Lassadi", "Alain Kamgoué", "Isabelle Goiffon", "Nicolas Tanguy-le-Gac", "Kerstin Bystricky"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1004306.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_type_specific_spatial_organization_of_the_three_mating_type_loci_on_yeast_chromosome_3_/1433156", "title"=>"Cell type specific spatial organization of the three mating type loci on yeast chromosome 3.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-01 04:42:02"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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