H3 K36 Methylation Helps Determine the Timing of Cdc45 Association with Replication Origins
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Mendeley | Further Information

{"title"=>"H3 K36 methylation helps determine the timing of Cdc45 association with replication origins", "type"=>"journal", "authors"=>[{"first_name"=>"Fiona", "last_name"=>"Pryde", "scopus_author_id"=>"6602600531"}, {"first_name"=>"Devanshi", "last_name"=>"Jain", "scopus_author_id"=>"57197487149"}, {"first_name"=>"Alastair", "last_name"=>"Kerr", "scopus_author_id"=>"17734953900"}, {"first_name"=>"Rebecca", "last_name"=>"Curley", "scopus_author_id"=>"57196922994"}, {"first_name"=>"Francesca Romana", "last_name"=>"Mariotti", "scopus_author_id"=>"57198146803"}, {"first_name"=>"Maria", "last_name"=>"Vogelauer", "scopus_author_id"=>"6506518636"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-67651245131", "sgr"=>"67651245131", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0005882", "pmid"=>"19521516", "isbn"=>"1932-6203", "pui"=>"354991687"}, "id"=>"547e38d8-c665-34c8-974a-079444381650", "abstract"=>"BACKGROUND: Replication origins fire at different times during S-phase. Such timing is determined by the chromosomal context, which includes the activity of nearby genes, telomeric position effects and chromatin structure, such as the acetylation state of the surrounding chromatin. Activation of replication origins involves the conversion of a pre-replicative complex to a replicative complex. A pivotal step during this conversion is the binding of the replication factor Cdc45, which associates with replication origins at approximately their time of activation in a manner partially controlled by histone acetylation. METHODOLOGY/PRINCIPAL FINDINGS: Here we identify histone H3 K36 methylation (H3 K36me) by Set2 as a novel regulator of the time of Cdc45 association with replication origins. Deletion of SET2 abolishes all forms of H3 K36 methylation. This causes a delay in Cdc45 binding to origins and renders the dynamics of this interaction insensitive to the state of histone acetylation of the surrounding chromosomal region. Furthermore, a decrease in H3 K36me3 and a concomitant increase in H3 K36me1 around the time of Cdc45 binding to replication origins suggests opposing functions for these two methylation states. Indeed, we find K36me3 depleted from early firing origins when compared to late origins genomewide, supporting a delaying effect of this histone modification for the association of replication factors with origins. CONCLUSIONS/SIGNIFICANCE: We propose a model in which K36me1 together with histone acetylation advance, while K36me3 and histone deacetylation delay, the time of Cdc45 association with replication origins. The involvement of the transcriptionally induced H3 K36 methylation mark in regulating the timing of Cdc45 binding to replication origins provides a novel means of how gene expression may affect origin dynamics during S-phase.", "link"=>"http://www.mendeley.com/research/h3-k36-methylation-helps-determine-timing-cdc45-association-replication-origins", "reader_count"=>56, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>19, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>19, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>40, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Business, Management and Accounting"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>40}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>2, "France"=>1, "Switzerland"=>1, "Estonia"=>1}, "group_count"=>1}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/894471"], "description"=>"<p>ChIP of MMY033 (WT), MVY51 (Δ<i>rpd3</i>), MVY57 (Δ<i>set2</i>) and MVY58 (Δ<i>rpd3</i>Δ<i>set2</i>) with antibodies specific for pan-acetylated histone H3 and H4 was performed. (A) Representative autoradiographs of PCR products using primer pairs specific for the indicated ARS elements and a telomeric loading control (TEL). (B) Graphic representation: Analysis was by semiquantitative PCR using primer pairs specific for indicated ARS elements and a telomeric loading control. The relative intensity of ARS specific fragments after normalization to the loading control and the input is presented. Errorbars refer to the standard deviation of the results of three independent experiments.</p>", "links"=>[], "tags"=>["histone", "acetylation"], "article_id"=>564928, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_916_set2_does_not_decrease_histone_acetylation_at_origins_/564928", "title"=>"<i>Δset2</i> does not decrease histone acetylation at origins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:22:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/895051"], "description"=>"<p>Replication factors have differential affinity for chromatin regions. Low affinity occurs at regions with low levels of histone acetylation and absence of K36me (silenced chromatin, left) and high levels of K36me3 (transcribed chromatin, right). High levels of K36me1 and histone acetylation cause high affinity for replication factors (center).</p>", "links"=>[], "tags"=>["histone", "modifications", "replication"], "article_id"=>565506, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_for_action_of_histone_modifications_at_replication_origins_/565506", "title"=>"Model for action of histone modifications at replication origins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:31:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/443537", "https://ndownloader.figshare.com/files/443573", "https://ndownloader.figshare.com/files/443603", "https://ndownloader.figshare.com/files/443634", "https://ndownloader.figshare.com/files/443670", "https://ndownloader.figshare.com/files/443699", "https://ndownloader.figshare.com/files/443733", "https://ndownloader.figshare.com/files/443767", "https://ndownloader.figshare.com/files/443835"], "description"=>"<div><h3>Background</h3><p>Replication origins fire at different times during S-phase. Such timing is determined by the chromosomal context, which includes the activity of nearby genes, telomeric position effects and chromatin structure, such as the acetylation state of the surrounding chromatin. Activation of replication origins involves the conversion of a pre-replicative complex to a replicative complex. A pivotal step during this conversion is the binding of the replication factor Cdc45, which associates with replication origins at approximately their time of activation in a manner partially controlled by histone acetylation.</p><h3>Methodology/Principal Findings</h3><p>Here we identify histone H3 K36 methylation (H3 K36me) by Set2 as a novel regulator of the time of Cdc45 association with replication origins. Deletion of <em>SET2</em> abolishes all forms of H3 K36 methylation. This causes a delay in Cdc45 binding to origins and renders the dynamics of this interaction insensitive to the state of histone acetylation of the surrounding chromosomal region. Furthermore, a decrease in H3 K36me3 and a concomitant increase in H3 K36me1 around the time of Cdc45 binding to replication origins suggests opposing functions for these two methylation states. Indeed, we find K36me3 depleted from early firing origins when compared to late origins genomewide, supporting a delaying effect of this histone modification for the association of replication factors with origins.</p><h3>Conclusions/Significance</h3><p>We propose a model in which K36me1 together with histone acetylation advance, while K36me3 and histone deacetylation delay, the time of Cdc45 association with replication origins. The involvement of the transcriptionally induced H3 K36 methylation mark in regulating the timing of Cdc45 binding to replication origins provides a novel means of how gene expression may affect origin dynamics during S-phase.</p></div>", "links"=>[], "tags"=>["h3", "k36", "methylation", "helps", "cdc45", "replication", "origins"], "article_id"=>147430, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0005882.s001", "https://dx.doi.org/10.1371/journal.pone.0005882.s002", "https://dx.doi.org/10.1371/journal.pone.0005882.s003", "https://dx.doi.org/10.1371/journal.pone.0005882.s004", "https://dx.doi.org/10.1371/journal.pone.0005882.s005", "https://dx.doi.org/10.1371/journal.pone.0005882.s006", "https://dx.doi.org/10.1371/journal.pone.0005882.s007", "https://dx.doi.org/10.1371/journal.pone.0005882.s008", "https://dx.doi.org/10.1371/journal.pone.0005882.s009"], "stats"=>{"downloads"=>17, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/H3_K36_Methylation_Helps_Determine_the_Timing_of_Cdc45_Association_with_Replication_Origins/147430", "title"=>"H3 K36 Methylation Helps Determine the Timing of Cdc45 Association with Replication Origins", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-06-12 02:03:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/894642"], "description"=>"<p>ChIP of MMY033 (WT) and MVY51 (Δrpd3) with antibodies specific for K36me1 (A) and −me3 (B). ChIP of strain MVY57 (Δ<i>set2</i>) is included as a negative control in (A). Representative autoradiographs of PCR products using primers specific for the indicated ARS elements and a telomeric loading control (TEL). The graph represents the average ratio (Δ<i>rpd3</i>/WT) of three independent experiments after normalization to input DNA and loading control. Error-bars refer to the standard deviations thereof.</p>", "links"=>[], "tags"=>["increases", "k36me"], "article_id"=>565096, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_916_rpd3_increases_K36me_at_some_but_not_all_origins_/565096", "title"=>"<i>Δrpd3</i> increases K36me at some but not all origins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/894744"], "description"=>"<p>(A) The ratio of K36me3/K36me1 for indicated ARSs is plotted against their time of activation and a linear trend-line was drawn. (B) ARSs are grouped for their time of firing in three minutes time intervals relative to the firing of the earliest ARS <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005882#pone.0005882-Raghuraman1\" target=\"_blank\">[6]</a>. ChIP on CHIP (Nimblegen) was used to determine genome-wide levels of H3 K36me3 and their distribution was determined for each group of ARSs and represented as box-plot. W- and P-values described in the text were calculated using the Wilcoxon rank sum test with continuity correction. (C) Same as in (B), but excluding all ARSs within 30 kb from chromosomal ends. (D) ChIP of MMY033 (WT) and MVY51 (Δ<i>rpd3</i>) with antibodies specific for K36me1 and −me3. Representative autoradiographs of PCR products using primers specific for the indicated ARS elements and a telomeric loading control (TEL). (E) Graphical representation of K36me1 or K36me3 ChIP showing the relative intensity of ARS-specific fragments after normalization to the loading control and the input. Complete lines indicate WT and broken lines indicate Δ<i>rpd3</i>.</p>", "links"=>[], "tags"=>["k36me3", "opposing", "behaviour", "dna", "replication"], "article_id"=>565196, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g005", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_K36me1_and_K36me3_show_opposing_behaviour_at_DNA_replication_origins_/565196", "title"=>"K36me1 and K36me3 show opposing behaviour at DNA replication origins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:26:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/894241"], "description"=>"<p>(A) Exponentially growing cells of strains MVY17 (WT), MVY31 (Δ<i>rpd3</i>), MVY37 (K36/37R) and MVY34 (Δ<i>rpd3</i>K36/37R) were arrested in G1 with α-factor and released into S-phase at 30°C. Samples were taken at indicated times and processed for FACS analysis. G1 and G2 DNA content are indicated at the bottom of the figure. Grey bars indicate the estimated length of S-phase. (B) Same as (A) but with strains MMY001 (WT), MMY002 (Δ<i>rpd3</i>), MVY42 (Δ<i>set2</i>) and MVY43 (Δ<i>rpd3</i>Δ<i>set2</i>).</p>", "links"=>[], "tags"=>["k36me", "set2", "accelerated", "s-phase", "progression"], "article_id"=>564687, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g001", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H3_K36me_by_Set2_is_necessary_for_accelerated_S_phase_progression_in_916_rpd3_cells_/564687", "title"=>"H3 K36me by Set2 is necessary for accelerated S-phase progression in <i>Δrpd3</i> cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/894363"], "description"=>"<p>Strains MMY033 (WT), MVY51 (Δ<i>rpd3</i>), MVY57 (Δ<i>set2</i>) and MVY58 (Δ<i>rpd3</i>Δ<i>set2</i>) were arrested in G1 with α-factor, released at 24°C into S-phase and samples were taken at indicated times. (A) Cell budding was assessed by microscopy. (B) ChIP of Cdc45-3FLAG was performed with an α-FLAG antibody and analysed by semiquantitative PCR using primers specific for ARS607, ARS1412 and a telomeric loading control (TEL). (C) Graphical representation of Cdc45-3FLAG ChIP showing the relative intensity of ARS-specific fragments after normalization to the telomeric loading control fragment and the input DNA. The time of maximal intensity is indicated for each strain.</p>", "links"=>[], "tags"=>["cdc45", "origins", "wt"], "article_id"=>564816, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g002", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Set2p_is_necessary_for_advanced_association_of_Cdc45_with_origins_in_WT_and_916_rpd3_cells_/564816", "title"=>"Set2p is necessary for advanced association of Cdc45 with origins in WT and <i>Δrpd3</i> cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:20:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/894900"], "description"=>"<p>(A) Strains MMY033 (WT), MVY51 (Δ<i>rpd3</i>), MVY54 (Δ<i>eaf3</i>) and MVY55 (Δ<i>eaf3</i>Δ<i>rpd3</i>) were arrested in G1 with α-factor and released into S-phase at 30°C. Samples were taken at indicated times and processed for FACS analysis. (B) as (A) with strains MMY001 (WT), MMY002 (Δ<i>rpd3</i>), MMY118 (Δ<i>nto1</i>) and MVY119 (Δ<i>rpd3</i>Δ<i>nto1</i>). (C) as (A) with strains MMY001 (WT), MMY002 (Δrpd3), MVY137 (Δ<i>eaf3</i>Δ<i>nto1</i>) and MVY138 (Δ<i>rpd3</i>Δ<i>eaf3</i>Δ<i>nto1</i>). Grey bars indicate the estimated length of S-phase. (D) Cell budding was assessed by microscopy. Complete lines indicate WT (black) and Δ<i>rpd3</i> (grey); broken lines indicate Δ<i>eaf3</i>Δ<i>nto1</i> (black) and Δ<i>rpd3</i>Δ<i>eaf3</i>Δ<i>nto1</i> (grey).</p>", "links"=>[], "tags"=>["s-phase"], "article_id"=>565352, "categories"=>["Molecular Biology", "Genetics"], "users"=>["Fiona Pryde", "Devanshi Jain", "Alastair Kerr", "Rebecca Curley", "Francesca Romana Mariotti", "Maria Vogelauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005882.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EAF3_and_NTO1_act_together_to_delay_S_phase_progression_/565352", "title"=>"<i>EAF3</i> and <i>NTO1</i> act together to delay S-phase progression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-12 01:29:12"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2009-01-01T00:00:00Z", "end_date"=>"2009-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[349, 614, 744, 851, 955, 1059, 1167, 1262, 1352, 1431, 1516, 1593, 1668, 1746, 1817, 1883, 1950, 2017, 2075, 2141, 2198, 2254, 2313, 2368, 2424, 2474, 2534, 2591, 2651, 2710, 2776, 2837, 2892, 2953, 3014, 3072, 3130, 3186, 3251, 3307, 3366, 3427, 3500, 3561, 3627, 3688, 3759, 3821, 3888, 3950, 4010, 4070, 4131, 4189, 4242, 4307, 4370, 4431, 4491, 4549, 4608]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[335, 600, 731, 835, 935, 1034, 1138, 1230, 1320, 1399, 1485, 1570, 1643, 1714, 1791, 1859, 1928, 1987, 2040, 2104, 2157, 2210, 2261, 2320, 2373, 2432, 2486, 2543, 2603, 2655, 2720, 2787, 2844, 2901, 2952, 3005, 3065, 3119, 3176, 3236, 3305, 3373, 3432, 3492, 3558, 3614, 3676, 3736, 3801, 3869, 3930, 3973, 4031, 4096, 4176, 4234, 4283, 4338, 4405, 4464, 4512]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[336, 588, 721, 826, 931, 1029, 1138, 1224, 1311, 1395, 1477, 1555, 1632, 1704, 1774, 1847, 1919, 1987, 2039, 2089, 2149, 2204, 2264, 2319, 2370, 2424, 2481, 2535, 2593, 2645, 2702, 2765, 2816, 2865, 2932, 2992, 3045, 3105, 3159, 3208, 3259, 3316, 3374, 3430, 3490, 3542, 3602, 3654, 3720, 3783, 3851, 3919, 3981, 4038, 4096, 4151, 4197, 4235, 4297, 4372, 4437]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[303, 516, 651, 762, 853, 944, 1048, 1140, 1218, 1291, 1366, 1449, 1509, 1593, 1663, 1726, 1797, 1856, 1906, 1958, 2018, 2083, 2128, 2175, 2235, 2294, 2354, 2403, 2452, 2502, 2558, 2617, 2672, 2730, 2794, 2857, 2913, 2970, 3036, 3087, 3155, 3216, 3270, 3336, 3390, 3450, 3508, 3568, 3623, 3705, 3762, 3812, 3895, 3938, 4026, 4083, 4137, 4187, 4235, 4292, 4348]}]}
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