TRF2 Controls Telomeric Nucleosome Organization in a Cell Cycle Phase-Dependent Manner
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{"title"=>"TRF2 controls telomeric nucleosome organization in a cell cycle phase-dependent manner", "type"=>"journal", "authors"=>[{"first_name"=>"Alessandra", "last_name"=>"Galati", "scopus_author_id"=>"7004266993"}, {"first_name"=>"Frédérique", "last_name"=>"Magdinier", "scopus_author_id"=>"18345214800"}, {"first_name"=>"Valentina", "last_name"=>"Colasanti", "scopus_author_id"=>"57190109364"}, {"first_name"=>"Serge", "last_name"=>"Bauwens", "scopus_author_id"=>"6603895738"}, {"first_name"=>"Sébastien", "last_name"=>"Pinte", "scopus_author_id"=>"6602588068"}, {"first_name"=>"Ruggero", "last_name"=>"Ricordy", "scopus_author_id"=>"6603013401"}, {"first_name"=>"Marie Josèphe", "last_name"=>"Giraud-Panis", "scopus_author_id"=>"6603278216"}, {"first_name"=>"Miriam Caroline", "last_name"=>"Pusch", "scopus_author_id"=>"55193220100"}, {"first_name"=>"Maria", "last_name"=>"Savino", "scopus_author_id"=>"55335927500"}, {"first_name"=>"Stefano", "last_name"=>"Cacchione", "scopus_author_id"=>"6602751441"}, {"first_name"=>"Eric", "last_name"=>"Gilson", "scopus_author_id"=>"24430764300"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84860010923", "doi"=>"10.1371/journal.pone.0034386", "issn"=>"19326203", "pui"=>"364661765", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"22536324", "scopus"=>"2-s2.0-84860010923"}, "id"=>"631721aa-d702-3fc8-ade0-f70c65b7cf55", "abstract"=>"Mammalian telomeres stabilize chromosome ends as a result of their assembly into a peculiar form of chromatin comprising a complex of non-histone proteins named shelterin. TRF2, one of the shelterin components, binds to the duplex part of telomeric DNA and is essential to fold the telomeric chromatin into a protective cap. Although most of the human telomeric DNA is organized into tightly spaced nucleosomes, their role in telomere protection and how they interplay with telomere-specific factors in telomere organization is still unclear. In this study we investigated whether TRF2 can regulate nucleosome assembly at telomeres.By means of chromatin immunoprecipitation (ChIP) and Micrococcal Nuclease (MNase) mapping assay, we found that the density of telomeric nucleosomes in human cells was inversely proportional to the dosage of TRF2 at telomeres. This effect was not observed in the G1 phase of the cell cycle but appeared coincident of late or post-replicative events. Moreover, we showed that TRF2 overexpression altered nucleosome spacing at telomeres increasing internucleosomal distance. By means of an in vitro nucleosome assembly system containing purified histones and remodeling factors, we reproduced the short nucleosome spacing found in telomeric chromatin. Importantly, when in vitro assembly was performed in the presence of purified TRF2, nucleosome spacing on a telomeric DNA template increased, in agreement with in vivo MNase mapping.Our results demonstrate that TRF2 negatively regulates the number of nucleosomes at human telomeres by a cell cycle-dependent mechanism that alters internucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization.", "link"=>"http://www.mendeley.com/research/trf2-controls-telomeric-nucleosome-organization-cell-cycle-phasedependent-manner", "reader_count"=>50, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>32, "Medicine and Dentistry"=>4, "Physics and Astronomy"=>2, "Chemistry"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>32}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "Italy"=>2, "United Kingdom"=>1, "France"=>1, "Australia"=>1, "India"=>2}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/649957"], "description"=>"<p>(<b>A</b>) Scheme of the synchronization experiment (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034386#s3\" target=\"_blank\">Materials and Methods</a> for details). (<b>B</b>) ChIP of C33A cells overexpressing TRF2<sup>FL</sup> and control C33A cells using the indicated antibodies and hybridized with Telo and Alu probes. From the left: slot-blots in asynchronous control cells; at the G1/S boundary; 5 hours after release from thymidine block; 12 hours after release; cells maintained in thymidine block for 12 additional hours (12 h+Th). (<b>C</b>) Quantifications of the data in (<b>B</b>) expressed as Telo/Alu hybridization signals. Error bars are s.d. of three independent experiments. Asterisks, p<0.05 based on unpaired Student's t-test.</p>", "links"=>[], "tags"=>["trf2-mediated", "telomeric"], "article_id"=>320437, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Alessandra Galati", "Frédérique Magdinier", "Valentina Colasanti", "Serge Bauwens", "Sébastien Pinte", "Ruggero Ricordy", "Marie-Josèphe Giraud-Panis", "Miriam Caroline Pusch", "Maria Savino", "Stefano Cacchione", "Eric Gilson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0034386.g003", "stats"=>{"downloads"=>4, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_cycle_regulation_of_TRF2_mediated_telomeric_remodelling_/320437", "title"=>"Cell-cycle regulation of TRF2-mediated telomeric remodelling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-20 00:07:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/649757"], "description"=>"<p>(<b>A</b>) ChIP of C33A cells overexpressing TRF2<sup>FL</sup> or TRF2<sup>ΔBΔM</sup> and control C33A cells using the indicated antibodies. Slot-blots were hybridized with a labelled Telo repeat probe and an Alu probe. (<b>B</b>) Quantification of the data in (<b>A</b>) expressed as probe/input hybridization signals. Error bars are s.d. of three independent experiments. Asterisks, p<0.05 based on unpaired Student's t-test.</p>", "links"=>[], "tags"=>["telomeres", "depends", "trf2"], "article_id"=>320238, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Alessandra Galati", "Frédérique Magdinier", "Valentina Colasanti", "Serge Bauwens", "Sébastien Pinte", "Ruggero Ricordy", "Marie-Josèphe Giraud-Panis", "Miriam Caroline Pusch", "Maria Savino", "Stefano Cacchione", "Eric Gilson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0034386.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nucleosome_density_at_human_telomeres_depends_on_TRF2_expression_/320238", "title"=>"Nucleosome density at human telomeres depends on TRF2 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-20 00:03:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/334105", "https://ndownloader.figshare.com/files/334128", "https://ndownloader.figshare.com/files/334160", "https://ndownloader.figshare.com/files/334192", "https://ndownloader.figshare.com/files/334219"], "description"=>"<div><p>Mammalian telomeres stabilize chromosome ends as a result of their assembly into a peculiar form of chromatin comprising a complex of non-histone proteins named shelterin. TRF2, one of the shelterin components, binds to the duplex part of telomeric DNA and is essential to fold the telomeric chromatin into a protective cap. Although most of the human telomeric DNA is organized into tightly spaced nucleosomes, their role in telomere protection and how they interplay with telomere-specific factors in telomere organization is still unclear. In this study we investigated whether TRF2 can regulate nucleosome assembly at telomeres.</p> <p>By means of chromatin immunoprecipitation (ChIP) and Micrococcal Nuclease (MNase) mapping assay, we found that the density of telomeric nucleosomes in human cells was inversely proportional to the dosage of TRF2 at telomeres. This effect was not observed in the G1 phase of the cell cycle but appeared coincident of late or post-replicative events. Moreover, we showed that TRF2 overexpression altered nucleosome spacing at telomeres increasing internucleosomal distance. By means of an <em>in vitro</em> nucleosome assembly system containing purified histones and remodeling factors, we reproduced the short nucleosome spacing found in telomeric chromatin. Importantly, when <em>in vitro</em> assembly was performed in the presence of purified TRF2, nucleosome spacing on a telomeric DNA template increased, in agreement with <em>in vivo</em> MNase mapping.</p> <p>Our results demonstrate that TRF2 negatively regulates the number of nucleosomes at human telomeres by a cell cycle-dependent mechanism that alters internucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization.</p> </div>", "links"=>[], "tags"=>["trf2", "controls", "telomeric", "nucleosome", "phase-dependent"], "article_id"=>125980, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Alessandra Galati", "Frédérique Magdinier", "Valentina Colasanti", "Serge Bauwens", "Sébastien Pinte", "Ruggero Ricordy", "Marie-Josèphe Giraud-Panis", "Miriam Caroline Pusch", "Maria Savino", "Stefano Cacchione", "Eric Gilson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0034386.s001", "https://dx.doi.org/10.1371/journal.pone.0034386.s002", "https://dx.doi.org/10.1371/journal.pone.0034386.s003", "https://dx.doi.org/10.1371/journal.pone.0034386.s004", "https://dx.doi.org/10.1371/journal.pone.0034386.s005"], "stats"=>{"downloads"=>4, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/TRF2_Controls_Telomeric_Nucleosome_Organization_in_a_Cell_Cycle_Phase_Dependent_Manner/125980", "title"=>"TRF2 Controls Telomeric Nucleosome Organization in a Cell Cycle Phase-Dependent Manner", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-20 01:39:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/650057"], "description"=>"<p>(<b>A</b>) MNase digestion of chromatin assembled on the 601/telomere DNA fragment. Lane 1, labelled 100 bp DNA ladder; lane 2 to 5, assembled chromatin digested respectively with 0, 2, 10, 60 U/ml of MNase. A schematic drawing of the DNA fragment and of the nucleosomal positioning and spacing is represented on the right. (<b>B</b>) MNase digestion of chromatin assembled on the 601-200<sub>8</sub> DNA fragment. Lane 1, labelled 100 bp DNA ladder; lane 2 to 3, assembled chromatin digested with MNase. (<b>C</b>) Chromatin assembly in the absence and in the presence of TRF2. Lane 1, labelled 100 bp DNA ladder; lane 2, assembled chromatin digested with 10 U/ml of MNase; lane 3, chromatin assembled in the presence of 100 nM TRF2 digested with 10 U/ml of MNase; lane 4, chromatin assembled in the presence of 200 nM TRF2 digested with 10 U/ml of MNase.</p>", "links"=>[], "tags"=>["chromatin", "telomeric"], "article_id"=>320540, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Alessandra Galati", "Frédérique Magdinier", "Valentina Colasanti", "Serge Bauwens", "Sébastien Pinte", "Ruggero Ricordy", "Marie-Josèphe Giraud-Panis", "Miriam Caroline Pusch", "Maria Savino", "Stefano Cacchione", "Eric Gilson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0034386.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TRF2_regulated_in_vitro_chromatin_assembly_on_human_telomeric_DNA_/320540", "title"=>"TRF2-regulated <i>in vitro</i> chromatin assembly on human telomeric DNA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-20 00:09:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/650184"], "description"=>"<p>See the text for details.</p>", "links"=>[], "tags"=>["trf2-induced", "remodeling", "telomeric"], "article_id"=>320662, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Alessandra Galati", "Frédérique Magdinier", "Valentina Colasanti", "Serge Bauwens", "Sébastien Pinte", "Ruggero Ricordy", "Marie-Josèphe Giraud-Panis", "Miriam Caroline Pusch", "Maria Savino", "Stefano Cacchione", "Eric Gilson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0034386.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Models_for_TRF2_induced_remodeling_of_telomeric_chromatin_/320662", "title"=>"Models for TRF2-induced remodeling of telomeric chromatin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-20 00:11:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/649851"], "description"=>"<p>(<b>A</b>) Digestion of chromatin from C33A cells infected with an empty vector and C33A cells overexpressing TRF2<sup>FL</sup> with increasing amounts of MNase. From the left: MNase digests separated on 1.5% agarose gel detected by hybridization with Telo probe; detection of telomeric nucleosomes after hybridization with Alu probe. (<b>B</b>) Ratio of the overall hybridization signal of the telomeric probe with respect to the Alu probe. Ratio values for control C33A cells have been normalized to 100. Error bars are s.d. of three independent experiments. Asterisks, p<0.05 based on unpaired Student's t-test.</p>", "links"=>[], "tags"=>["nucleosome", "spacing", "c33a"], "article_id"=>320338, "categories"=>["Molecular Biology", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Alessandra Galati", "Frédérique Magdinier", "Valentina Colasanti", "Serge Bauwens", "Sébastien Pinte", "Ruggero Ricordy", "Marie-Josèphe Giraud-Panis", "Miriam Caroline Pusch", "Maria Savino", "Stefano Cacchione", "Eric Gilson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0034386.g002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Altered_nucleosome_spacing_at_C33A_telomeres_/320338", "title"=>"Altered nucleosome spacing at C33A telomeres.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-20 00:05:38"}

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Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[319, 556, 679, 785, 881, 970, 1062, 1149, 1236, 1323, 1402, 1474, 1545, 1617, 1681, 1754, 1822, 1892, 1963, 2031, 2099, 2165, 2233, 2299, 2359]}]}
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