H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation
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{"title"=>"H4K20me1 Contributes to Downregulation of X-Linked Genes for C. elegans Dosage Compensation", "type"=>"journal", "authors"=>[{"first_name"=>"Anne", "last_name"=>"Vielle", "scopus_author_id"=>"22959151500"}, {"first_name"=>"Jackie", "last_name"=>"Lang", "scopus_author_id"=>"55370978000"}, {"first_name"=>"Yan", "last_name"=>"Dong", "scopus_author_id"=>"7403390609"}, {"first_name"=>"Sevinc", "last_name"=>"Ercan", "scopus_author_id"=>"14719493400"}, {"first_name"=>"Chitra", "last_name"=>"Kotwaliwale", "scopus_author_id"=>"12242253400"}, {"first_name"=>"Andreas", "last_name"=>"Rechtsteiner", "scopus_author_id"=>"14625456600"}, {"first_name"=>"Alex", "last_name"=>"Appert", "scopus_author_id"=>"6602281646"}, {"first_name"=>"Q. Brent", "last_name"=>"Chen", "scopus_author_id"=>"55814355200"}, {"first_name"=>"Andrea", "last_name"=>"Dose", "scopus_author_id"=>"6603926383"}, {"first_name"=>"Thea", "last_name"=>"Egelhofer", "scopus_author_id"=>"16300824900"}, {"first_name"=>"Hiroshi", "last_name"=>"Kimura", "scopus_author_id"=>"56735099000"}, {"first_name"=>"Przemyslaw", "last_name"=>"Stempor", "scopus_author_id"=>"55371040900"}, {"first_name"=>"Abby", "last_name"=>"Dernburg", "scopus_author_id"=>"6603945120"}, {"first_name"=>"Jason D.", "last_name"=>"Lieb", "scopus_author_id"=>"7005815585"}, {"first_name"=>"Susan", "last_name"=>"Strome", "scopus_author_id"=>"7004882319"}, {"first_name"=>"Julie", "last_name"=>"Ahringer", "scopus_author_id"=>"7004726748"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "pui"=>"365755979", "doi"=>"10.1371/journal.pgen.1002933", "sgr"=>"84866914821", "scopus"=>"2-s2.0-84866914821", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"23028348"}, "id"=>"752e692e-a875-3d29-b555-a84b45ad4593", "abstract"=>"The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of set-1 results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like C. elegans DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction.", "link"=>"http://www.mendeley.com/research/h4k20me1-contributes-downregulation-xlinked-genes-c-elegans-dosage-compensation", "reader_count"=>66, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>19, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>19, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>14, "Agricultural and Biological Sciences"=>45, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>45}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Norway"=>1, "Japan"=>1, "United Kingdom"=>2, "Switzerland"=>3}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/304161", "https://ndownloader.figshare.com/files/304219", "https://ndownloader.figshare.com/files/304288", "https://ndownloader.figshare.com/files/304376", "https://ndownloader.figshare.com/files/304482", "https://ndownloader.figshare.com/files/304558", "https://ndownloader.figshare.com/files/304619", "https://ndownloader.figshare.com/files/304680"], "description"=>"<div><p>The <em>Caenorhabditis elegans</em> dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of <em>set-1</em> results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like <em>C. elegans</em> DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction.</p> </div>", "links"=>[], "tags"=>["h4k20me1", "contributes", "downregulation", "x-linked", "genes", "dosage"], "article_id"=>119992, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.s001", "https://dx.doi.org/10.1371/journal.pgen.1002933.s002", "https://dx.doi.org/10.1371/journal.pgen.1002933.s003", "https://dx.doi.org/10.1371/journal.pgen.1002933.s004", "https://dx.doi.org/10.1371/journal.pgen.1002933.s005", "https://dx.doi.org/10.1371/journal.pgen.1002933.s006", "https://dx.doi.org/10.1371/journal.pgen.1002933.s007", "https://dx.doi.org/10.1371/journal.pgen.1002933.s008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/H4K20me1_Contributes_to_Downregulation_of_X_Linked_Genes_for_C_elegans_Dosage_Compensation/119992", "title"=>"H4K20me1 Contributes to Downregulation of X-Linked Genes for <em>C. elegans</em> Dosage Compensation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-13 02:46:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/576659"], "description"=>"<p>(A) Genome browser tracks of indicated ChIP signals across representative regions of chromosome I and chromosome X in wild-type early embryos (EE), late embryos (LE), L3 larvae (L3), and <i>fem-2</i> female young adults (YA). For each track, the average of two independent biological replicates is shown as z-scores (standardized log<sub>2</sub> ratios of ChIP/Input signals). High H4K20me1 enrichment on X begins in late embryos. A track of DPY-27 (a DCC component) is shown for reference. (B) Enrichment of H4K20me1 on the X is lost in <i>dpy-21</i> mutants. (C) Plots of H4K20me1 and H4K20me3 signal across the TSS (transcript start site) and TES (transcript end site) of genes on X (red) and autosomes (blue). Genes in the top 20% of expression (dark shades) and bottom 20% (light shades) are plotted separately. (D) Plots of H4K20me1 and H4K20me3 signal centered at intergenic regions at least 5 kb from any annotated feature. (E) Box plots of overall H4K20me1 and H4K20me3 signals on each chromosome. Each box shows the median and extends from the 25<sup>th</sup> to the 75<sup>th</sup> percentile of the z-scores in the set; whiskers extending from the box indicate the 2.5<sup>th</sup> and 97.5<sup>th</sup> percentiles.</p>", "links"=>[], "tags"=>["becomes", "enriched", "chromosome", "mutant", "defective", "dosage"], "article_id"=>247115, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H4K20me1_becomes_enriched_on_the_X_chromosome_in_wild_type_but_not_in_a_mutant_defective_in_dosage_compensation_/247115", "title"=>"H4K20me1 becomes enriched on the X chromosome in wild type but not in a mutant defective in dosage compensation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-13 01:58:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/576887"], "description"=>"<p>Wild-type embryos at (A) 20-cell, (B) 40-cell, (C) bean, (D) comma, and (E) three-fold stages stained for DNA (DAPI, blue, left column), DPY-27 (red, second column), and H4K20me1 (green, third column). Boxed regions in B and E are enlarged in F and G, respectively. In very early embryos (A) DPY-27 exhibits weak and diffuse nuclear staining while H4K20me1 is diffuse in interphase nuclei and associated with condensed chromatin during mitosis. By the ∼40-cell stage (B, F) DPY-27 is enriched on the X chromosome, while H4K20me1 continues to show a uniform nuclear distribution. Comma-stage embryos (D) contain some nuclei with H4K20me1 enrichment on the X. This enrichment becomes more apparent as embryogenesis progresses, and by the 3-fold stage (E, G) H4K20me1 is concentrated in bright foci that co-localize with DPY-27 on the X. Scale bars represent 10 um (A–E) and 2 um (F, G). Monoclonal antibody15F11 was used to detect H4K20me1.</p>", "links"=>[], "tags"=>["becomes", "concentrated", "chromosome"], "article_id"=>247356, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H4K20me1_becomes_concentrated_on_the_X_chromosome_after_the_DCC_/247356", "title"=>"H4K20me1 becomes concentrated on the X chromosome after the DCC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-13 02:02:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/577075"], "description"=>"<p>H4K20me1 ChIPs were performed in wild-type (WT) and YPT41 mixed stage embryos. YPT41 carries a fusion of the right end of X to the left end of chromosome II. The fusion site is indicated with a dashed line. DPY-27 ChIP-chip and H4K20me1 ChIP-seq enrichment are shown in blue and black, respectively. For each track, the average of two independent biological replicates is shown as z-scores (standardized log<sub>2</sub> ratios of ChIP/Input signals). Genome browser views of ∼2 Mb and ∼200 kb spanning the fusion site are shown on the top and below, respectively.</p>", "links"=>[], "tags"=>["ectopically", "spreads", "autosomal", "fusion"], "article_id"=>247543, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H4K20me1_ectopically_spreads_onto_the_autosomal_region_of_an_X_II_fusion_chromosome_/247543", "title"=>"H4K20me1 ectopically spreads onto the autosomal region of an X;II fusion chromosome.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-13 02:05:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/577224"], "description"=>"<p>Three-fold embryos were stained with DAPI and antibodies to DPY-27 and H4K20me1. (A) Wild-type (WT) XX hermaphrodite, (B) <i>him-8</i> XO male, (C) <i>dpy-30(y228)</i> (D) <i>dpy-28(y1)</i>, (E) <i>dpy-26(n199)</i>, and (F) <i>dpy-21(e428)</i> hermaphrodites. Left panel shows whole embryos, right panels show enlargements of nuclei. Foci of H4K20me1 X-chromosome enrichment are absent in males and dosage compensation mutants. Scale bars represent 10 um (left column) and 2 um (enlargements). Monoclonal antibody 15F11 antibody was used to detect H4K20me1.</p>", "links"=>[], "tags"=>["enrichment", "chromosome", "depends", "dosage"], "article_id"=>247691, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_H4K20me1_enrichment_to_the_X_chromosome_depends_on_dosage_compensation_/247691", "title"=>"H4K20me1 enrichment to the X chromosome depends on dosage compensation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-13 02:08:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/577404"], "description"=>"<p>(A) Embryos were stained with DAPI and antibodies to DPY-27 and H4K20me1. In <i>set-1/hT2G</i> embryos (identified by pharyngeal GFP signal from the <i>hT2G</i> balancer chromosome), DPY-27 and H4K20me1 are enriched on the X chromosome. In homozygous <i>set-1</i> mutant embryos, DPY-27 is enriched on the X, but H4K20me1 is undetectable. Scale bar represents 10 um. (B) Western blots of H4K20me1, H4K20me2, and H4K20me3 in wild-type (WT) and <i>set-1(tm1821)</i> mutant adults. The loading control is histone H3. SET-1 protein is not detected in <i>set-1</i> mutant extract. (C) Tests of genetic interactions with dosage compensation mutants. Shown is % embryonic lethality of wild type (WT), <i>dpy-21(e428)</i> and <i>dpy-28(y1ts)</i> mutants after RNAi of the indicated gene. RNAi was performed by feeding as described in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002933#s4\" target=\"_blank\">Methods</a>. (D) Expression of autosomal genes in blue (W07G4.4 and act-1) and X-linked genes in red (<i>aco-1</i>, <i>ajm-1</i>, and <i>apl-1</i>) in the indicated mutants relative to wild-type. Expression levels are normalized to autosomal gene W07G4.4. Error bars show 95% confidence intervals.</p>", "links"=>[], "tags"=>["h4k20me1", "methyltransferase", "set-1", "genetically", "interacts", "dosage", "mutants", "repression", "x-linked"], "article_id"=>247855, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_H4K20me1_methyltransferase_SET_1_genetically_interacts_with_dosage_compensation_mutants_and_is_required_for_repression_of_X_linked_gene_expression_/247855", "title"=>"The H4K20me1 methyltransferase SET-1 genetically interacts with dosage compensation mutants and is required for repression of X-linked gene expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-13 02:10:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/577513"], "description"=>"<p>(A) Wild-type (WT) and <i>set-4(n4600)</i> mutant embryos were stained for DNA (DAPI), and H4K20me1, H4K20me2, or H4K20me3. H420me1 levels are higher and H4K20me2 and H4K20me3 levels strongly reduced in <i>set-4</i> mutant embryos. Scale bar, 10 um. (B) Enlargements of nuclei in wild-type and <i>set-4(n4600)</i> mutant embryos stained for DNA (DAPI), H4K20me1, and DPY-27. In <i>set-4</i> embryos, H4K20me1 does not show enrichment in DPY-27 positive regions. Confocal settings for H4K20me1 in <i>set-4</i> were reduced to allow comparison with wild-type images. Scale bar, 2 um. (C) Western blots of extracts made from wild-type and <i>set-4</i> adults, probed for H4K20me1, H420me2, or H4K20me3. Histone H3 is a loading control. Compared to wild type, <i>set-4</i> mutants have increased H4K20me1 levels, and reduced H4K20me2 and H4K20me3 levels. (D, E) Western blots of H4K20me1 (D) and H4K20me3 (E) in wild-type and <i>dpy-21</i> L3 mutant extracts. Lower panels show H3 loading controls. (D) H4K20me1 abundance is lower in <i>dpy-21</i> than in wild type. (E) H4K20me3 abundance is higher in <i>dpy-21</i> mutant L3 extract than in wild type. In (D) RNAi of <i>set-4</i> was additionally performed. H4K20me1 abundance is elevated in both wild-type and <i>dpy-21</i> after depletion of <i>set-4</i>. The following primary antibodies were used: H4K20me1 (Diagenode SN-147), H420me2 (Kimura 2E2), H4K20me3 (Abcam ab78517).</p>", "links"=>[], "tags"=>["set-4", "histone", "methyltransferase", "h4k20me2"], "article_id"=>247978, "categories"=>["Biological Sciences"], "users"=>["Anne Vielle", "Jackie Lang", "Yan Dong", "Sevinc Ercan", "Chitra Kotwaliwale", "Andreas Rechtsteiner", "Alex Appert", "Q. Brent Chen", "Andrea Dose", "Thea Egelhofer", "Hiroshi Kimura", "Przemyslaw Stempor", "Abby Dernburg", "Jason D. Lieb", "Susan Strome", "Julie Ahringer"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002933.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_SET_4_histone_methyltransferase_is_necessary_to_generate_H4K20me2_and_H4K20me3_/247978", "title"=>"The SET-4 histone methyltransferase is necessary to generate H4K20me2 and H4K20me3.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-13 02:12:58"}

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Relative Metric

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