STAT Is an Essential Activator of the Zygotic Genome in the Early Drosophila Embryo
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{"title"=>"STAT is an essential activator of the zygotic genome in the early drosophila embryo", "type"=>"journal", "authors"=>[{"first_name"=>"Amy", "last_name"=>"Tsurumi", "scopus_author_id"=>"24367538300"}, {"first_name"=>"Fan", "last_name"=>"Xia", "scopus_author_id"=>"57197924420"}, {"first_name"=>"Jinghong", "last_name"=>"Li", "scopus_author_id"=>"26663614400"}, {"first_name"=>"Kimberly", "last_name"=>"Larson", "scopus_author_id"=>"24173193600"}, {"first_name"=>"Russell", "last_name"=>"LaFrance", "scopus_author_id"=>"56627188200"}, {"first_name"=>"Willis X.", "last_name"=>"Li", "scopus_author_id"=>"7501787633"}], "year"=>2011, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-79957990336", "pui"=>"361887811", "doi"=>"10.1371/journal.pgen.1002086", "isbn"=>"1553-7390 (Print)1553-7404 (Electronic)", "sgr"=>"79957990336", "pmid"=>"21637778"}, "id"=>"cba8c0d5-86b3-3731-a765-671d96a88fc5", "abstract"=>"In many organisms, transcription of the zygotic genome begins during the maternal-to-zygotic transition (MZT), which is characterized by a dramatic increase in global transcriptional activities and coincides with embryonic stem cell differentiation. In Drosophila, it has been shown that maternal morphogen gradients and ubiquitously distributed general transcription factors may cooperate to upregulate zygotic genes that are essential for pattern formation in the early embryo. Here, we show that Drosophila STAT (STAT92E) functions as a general transcription factor that, together with the transcription factor Zelda, induces transcription of a large number of early-transcribed zygotic genes during the MZT. STAT92E is present in the early embryo as a maternal product and is active around the MZT. DNA-binding motifs for STAT and Zelda are highly enriched in promoters of early zygotic genes but not in housekeeping genes. Loss of Stat92E in the early embryo, similarly to loss of zelda, preferentially down-regulates early zygotic genes important for pattern formation. We further show that STAT92E and Zelda synergistically regulate transcription. We conclude that STAT92E, in conjunction with Zelda, plays an important role in transcription of the zygotic genome at the onset of embryonic development.", "link"=>"http://www.mendeley.com/research/stat-essential-activator-zygotic-genome-early-drosophila-embryo", "reader_count"=>51, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>3, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>3, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>35, "Neuroscience"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>35}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}}, "reader_count_by_country"=>{"United States"=>3, "Mexico"=>1, "France"=>2, "Russia"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/771165"], "description"=>"<p>(A) Schematic representation of the <i>dpp</i> reporter\n constructs with two STAT-binding sites (red triangles; STAT1 and STAT2)\n and a Zelda binding site (gray arrowhead). Sequence differences between\n wild-type (WT) and double-mutant (DM) constructs are noted. Arrows\n represent primers for PCR amplification used in ChIP experiments.\n Sequences of STAT and Zelda binding sites and the corresponding mutants\n are shown. (B) <i>Drosophila</i> S2 cells were transfected\n with V5-tagged STAT92E, with or without V5-Hop. Cell lysates were\n subjected to SDS-PAGE and blotted with indicated antibodies. Note that\n cotransfection of Hop induces phosphorylation of STAT92E in S2 cells\n (lane 3). (C, E) Chromatin immunoprecipitation (ChIP) experiments to\n detect binding of STAT92E and Zelda to <i>dpp</i> promoter. S2\n cells were transfected with V5-STAT92E with or without Hop, as indicated\n (C), or with Flag-Zelda (E). Anti-V5 or anti-Flag were used to\n immunoprecipitate STAT92E or Zelda, respectively. The chromatin in the\n immunoprecipitates was detected by PCR with primers used in (A). Note\n that the <i>dpp</i> promoter fragment bound to STAT92E is more\n enriched when Hop is coexpressed (C; lane 3), and that Zelda is enriched\n in the <i>dpp</i> promoter (E; lane 2). Quantification using\n real-time PCR is shown in lower panel. (D, F) S2 cells were transfected\n with <i>dpp<sup>WT</sup></i>-luc or\n <i>dpp<sup>DM</sup></i>-luc, and cotransfected with Hop\n and STAT (D), or additionally with or without Zelda (F). Hop, STAT, and\n Zelda were under the control of a metallothionein (MT) promoter.\n Relative luciferase activity was measured at indicated hours (D) or at\n 72 hours (F) after induction of the MT promoter by CuSO<sub>4</sub>.\n Results of three independent experiments are shown. Note that in\n <i>dpp<sup>WT</sup></i>-luc cells, STAT activation\n resulted in >20-fold increase in luciferase activity at 72 h after\n induction (D), Zelda expression resulted in a 50 fold increase in\n luciferase activity (F, colume 3), and that in presence of activated\n STAT and co-transfected Zelda, there was >200 fold increase in\n luciferase activity (F, colume 4).</p>", "links"=>[], "tags"=>["zelda", "synergistically", "regulates", "s2"], "article_id"=>441530, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002086.g004", "stats"=>{"downloads"=>3, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_STAT92E_and_Zelda_synergistically_regulates_dpp____reporter_gene_expression_in_Drosophila_S2____cells_/441530", "title"=>"STAT92E and Zelda synergistically regulates <i>dpp</i>\n reporter gene expression in <i>Drosophila</i> S2\n cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-26 00:25:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/770921"], "description"=>"<p>RNA isolated from 1–2 h wild-type and\n <i>Stat92E<sup>mat–</sup></i> embryos were\n subjected to microarray analysis. (A) Summary of expression profiles of\n <i>Stat92E<sup>mat–</sup></i> versus wild-type\n embryos. (B) Percent of genes categorized as zygotic (Z), maternal (M),\n or both (M/Z) in the down-regulated (≥2-fold;\n n = 657) or up-regulated (≥2-fold;\n n = 558) sets. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002086#pgen.1002086.s004\" target=\"_blank\">Figure\n S4</a>, <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002086#pgen.1002086.s005\" target=\"_blank\">Figure S5</a> for the complete list of Z,\n M, and M/Z genes. Note that 78.2% of down-regulated genes belong\n to “zygotic genes”, whereas there are more maternal than\n “zygotic genes” present in the up-regulated set. (C) Fold\n changes in the expression of the listed zygotic and housekeeping genes\n in <i>Stat92E<sup>mat–</sup></i> versus wild-type\n embryos based on the microarray analysis. Average changes and p values\n (Student's t-Test) are shown. (D) The expression values of a set of\n 40 “zygotic” and 40 housekeeping genes from the microarray\n analysis were used for Gene Set Enrichment Analysis (GSEA). See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002086#pgen.1002086.s013\" target=\"_blank\">Table\n S6</a> for gene names and expression values. Normalized\n enrichment scores (NESs) and p-values are shown. Note that the\n “zygotic genes” show highly significant concordant down\n regulation, whereas the housekeeping genes show insignificant\n changes.</p>", "links"=>[], "tags"=>["profiles", "embryos", "lacking", "maternal"], "article_id"=>441287, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002086.g002", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_profiles_of_embryos_lacking_maternal_STAT92E_/441287", "title"=>"Expression profiles of embryos lacking maternal STAT92E.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-26 00:21:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/771003"], "description"=>"<p>(A) Total RNA was isolated from staged early embryos (1–2 h after\n egg laying) of the indicated genotypes, and mRNA levels of\n <i>dpp</i>, <i>Kr</i>, <i>tll</i>, and\n <i>eve</i> were measured relative to those of\n <i>rp49</i> (control) by semi-quantitative RT-PCR. A\n representative gel picture is shown. (B) Quantification of the RT-PCR\n results. Note that the levels of <i>dpp</i>,\n <i>Kr</i>, <i>tll</i>, and <i>eve</i>\n mRNA were higher in <i>hop<sup>Tum-l/+</sup></i> embryos,\n lower in <i>Stat92E<sup>mat–</sup></i> embryos, and were\n further reduced when combined with\n <i>zld<sup>+/–</sup></i>. (C) Levels of mRNA\n expression in embryos of indicated genotypes were quantified by\n real-time PCR. Error bars indicate standard deviation. (D) Early\n wild-type embryos (1–2 h AEL) were homogenized and used for ChIP\n experiments with goat anti-STAT92E. An equal amount of goat IgG was used\n as control. The <i>Stat92E</i> promoter was used as a positive\n control, and the rp49 promoter as a negative control.</p>", "links"=>[], "tags"=>["signaling", "regulates"], "article_id"=>441373, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002086.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_JAK_STAT_signaling_regulates_multiple_8220_zygotic____genes_8221_/441373", "title"=>"JAK/STAT signaling regulates multiple “zygotic\n genes.”", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-26 00:22:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/770801"], "description"=>"<p>(A) Activation scores for transcription factors or signaling pathways\n important for transcriptional upregulation of a set of 21 zygotically\n expressed genes. The top eight factors are indicated. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002086#pgen.1002086.s009\" target=\"_blank\">Table\n S2</a> for a complete list of factors and their scores. (B) An\n activation map showing connections between activators (top row) and\n their target genes, grouped as gap genes, pair-rule genes, segment\n polarity genes, and genes expressed along the D/V axis. Lines indicate\n activation (some are indirect). The thickness of the line represents the\n activation strength based on meta-analysis. (C, D) Horizontal lines\n represent promoter regions of the indicated early zygotic genes (C) or\n housekeeping genes (D). Numbers indicate base pairs upstream (–)\n of the transcriptional start site (0). Red triangles represent consensus\n STAT92E binding sites (TTCnnnGAA). Gray arrowheads indicate the\n positions of Zelda-binding consensus sequences (CAGGTAG). Bold gene\n names indicate the promoter regions as shown are known to support\n expression. A list of additional housekeeping genes can be found in\n <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002086#pgen.1002086.s010\" target=\"_blank\">Table S3</a>.</p>", "links"=>[], "tags"=>["contributing", "zygotic", "the"], "article_id"=>441166, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002086.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Factors_contributing_to_zygotic_gene_expression_during_the____MZT_/441166", "title"=>"Factors contributing to zygotic gene expression during the\n MZT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-26 00:19:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/771353"], "description"=>"<p>Dark-field images of larval cuticles of different genotypes are shown,\n with anterior to the left. The position of the sixth abdominal denticle\n belt is marked as A6. (A) A ventral view of a wild-type larval cuticle,\n with eight abdominal denticle belts seen in the ventral region, spanning\n <50% of the body circumference. The arrow points to the\n Filzkörper, a terminal element. (B)\n <i>Stat92E<sup>mat–</sup></i> cuticle exhibits\n defects in central elements (A4, 5) and minor defects in the posterior\n region, but does not show overt D/V polarity defects. Note that the\n Filzkörper is present (arrow). (C)\n <i>tll<sup>–/–</sup></i> embryos are\n missing posterior terminal structures (A8 and the Filzkörper). (D)\n <i>Stat92E<sup>mat–</sup></i>;\n <i>tll<sup>+/–</sup></i> embryos lack\n posterior terminal structures (A7/8 and the Filzkörper), similar to\n <i>tll<sup>–/–</sup></i> embryos. (E)\n <i>Kr<sup>–/–</sup></i> embryos exhibit\n anterior defects, lacking or having fused A1–5 ventral deticle\n bands. (F) <i>Stat92E<sup>mat–</sup></i>;\n <i>Kr<sup>+/–</sup></i> embryos are missing\n many anterior denticle bands, reminiscent of\n <i>Kr<sup>–/–</sup></i> embryos. (G)\n <i>dpp<sup>–/–</sup></i> larvae are\n ventralized, with denticle belts around the whole body circumference.\n (H) A portion of <i>State92E<sup>mat–</sup></i>;\n <i>dpp<sup>+/–</sup></i> larvae are\n partially ventralized, with posterior denticle belts (usually A6; arrow)\n extended to the dorsal side, encompassing 80% of the body\n circumference.</p>", "links"=>[], "tags"=>["lacking", "cuticle", "morphology", "of"], "article_id"=>441721, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002086.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_lacking_Stat92E_on_cuticle_morphology_of____embryos_/441721", "title"=>"Effects of lacking <i>Stat92E</i> on cuticle morphology of\n embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-26 00:28:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/387086", "https://ndownloader.figshare.com/files/387119", "https://ndownloader.figshare.com/files/387145", "https://ndownloader.figshare.com/files/387174", "https://ndownloader.figshare.com/files/387197", "https://ndownloader.figshare.com/files/387228", "https://ndownloader.figshare.com/files/387250", "https://ndownloader.figshare.com/files/387275", "https://ndownloader.figshare.com/files/387291", "https://ndownloader.figshare.com/files/387306", "https://ndownloader.figshare.com/files/387318", "https://ndownloader.figshare.com/files/387338", "https://ndownloader.figshare.com/files/387353"], "description"=>"<div><p>In many organisms, transcription of the zygotic genome begins during the maternal-to-zygotic transition (MZT), which is characterized by a dramatic increase in global transcriptional activities and coincides with embryonic stem cell differentiation. In <em>Drosophila</em>, it has been shown that maternal morphogen gradients and ubiquitously distributed general transcription factors may cooperate to upregulate zygotic genes that are essential for pattern formation in the early embryo. Here, we show that <em>Drosophila</em> STAT (STAT92E) functions as a general transcription factor that, together with the transcription factor Zelda, induces transcription of a large number of early-transcribed zygotic genes during the MZT. STAT92E is present in the early embryo as a maternal product and is active around the MZT. DNA–binding motifs for STAT and Zelda are highly enriched in promoters of early zygotic genes but not in housekeeping genes. Loss of <em>Stat92E</em> in the early embryo, similarly to loss of <em>zelda</em>, preferentially down-regulates early zygotic genes important for pattern formation. We further show that STAT92E and Zelda synergistically regulate transcription. We conclude that STAT92E, in conjunction with Zelda, plays an important role in transcription of the zygotic genome at the onset of embryonic development.</p> </div>", "links"=>[], "tags"=>["stat", "activator", "zygotic", "genome", "early", "embryo"], "article_id"=>136420, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002086.s001", "https://dx.doi.org/10.1371/journal.pgen.1002086.s002", "https://dx.doi.org/10.1371/journal.pgen.1002086.s003", "https://dx.doi.org/10.1371/journal.pgen.1002086.s004", "https://dx.doi.org/10.1371/journal.pgen.1002086.s005", "https://dx.doi.org/10.1371/journal.pgen.1002086.s006", "https://dx.doi.org/10.1371/journal.pgen.1002086.s007", "https://dx.doi.org/10.1371/journal.pgen.1002086.s008", "https://dx.doi.org/10.1371/journal.pgen.1002086.s009", "https://dx.doi.org/10.1371/journal.pgen.1002086.s010", "https://dx.doi.org/10.1371/journal.pgen.1002086.s011", "https://dx.doi.org/10.1371/journal.pgen.1002086.s012", "https://dx.doi.org/10.1371/journal.pgen.1002086.s013"], "stats"=>{"downloads"=>51, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/STAT_Is_an_Essential_Activator_of_the_Zygotic_Genome_in_the_Early____Drosophila_Embryo/136420", "title"=>"STAT Is an Essential Activator of the Zygotic Genome in the Early\n <em>Drosophila</em> Embryo", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-05-26 01:47:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/771290"], "description"=>"<p>Expression patterns and levels of <i>dpp, Kr</i>, and\n <i>tll</i> mRNA or Kr protein (dark stain) were detected\n by in situ hybridization in precellularization or cellularization stage\n wild-type (left) and <i>Stat92E<sup>mat–</sup></i>\n (right) embryos. Stainings were carried out in parallel under identical\n conditions. Developmental stage was identified by nuclear density,\n visualized with DAPI stain. Representative embryo images are shown. All\n embryos are shown with anterior to the left and dorsal up. (A, B)\n <i>dpp</i> expression at the cellularization stage. In\n wild-type embryos (A), <i>dpp</i> mRNA is expressed in the\n dorsal and posterior regions. In\n <i>Stat92E<sup>mat–</sup></i> embryos (B),\n <i>dpp</i> expression is much reduced, especially at the\n posterior pole region. (C, D) Expression of <i>Kr</i> mRNA in\n precellularization stage embryos. Note that in\n <i>Stat92E<sup>mat–</sup></i> embryos,\n <i>Kr</i> mRNA is expressed in the correct domain but in\n much reduced levels. (E, F) <i>tll</i> mRNA expression at the\n cellularization stage. Note that in\n <i>Stat92E<sup>mat–</sup></i> embryos,\n <i>tll</i> is expressed in the correct domains but at\n lower levels.</p>", "links"=>[], "tags"=>["lacking", "of", "early"], "article_id"=>441663, "categories"=>["Developmental Biology"], "users"=>["Amy Tsurumi", "Fan Xia", "Jinghong Li", "Kimberly Larson", "Russell LaFrance", "Willis X. Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002086.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_lacking_Stat92E_on_expression_of_____dpp_Kr_and_tll_in_early____embryos_/441663", "title"=>"Effects of lacking <i>Stat92E</i> on expression of\n <i>dpp, Kr</i>, and <i>tll</i> in early\n embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-26 00:27:43"}

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