Evx2-Hoxd13 Intergenic Region Restricts Enhancer Association to Hoxd13 Promoter
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{"title"=>"Evx2-Hoxd13 intergenic region restricts enhancer association to Hoxd13 promoter", "type"=>"journal", "authors"=>[{"first_name"=>"Takumi", "last_name"=>"Yamagishi", "scopus_author_id"=>"35739391500"}, {"first_name"=>"Michiru", "last_name"=>"Ozawa", "scopus_author_id"=>"16029439300"}, {"first_name"=>"Chiho", "last_name"=>"Ohtsuka", "scopus_author_id"=>"22941565400"}, {"first_name"=>"Ritsuko", "last_name"=>"Ohyama-Goto", "scopus_author_id"=>"16028738100"}, {"first_name"=>"Takashi", "last_name"=>"Kondo", "scopus_author_id"=>"55972175400"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"352599026", "sgr"=>"41849133934", "pmid"=>"17245451", "scopus"=>"2-s2.0-41849133934", "doi"=>"10.1371/journal.pone.0000175"}, "id"=>"cc3d01ba-c786-3f18-b511-a2ae9d42c11e", "abstract"=>"Expression of Hox genes is tightly regulated in spatial and temporal domains. Evx2 is located next to Hoxd13 within 8 kb on the opposite DNA strand. Early in development, the pattern of Hoxd13 expression resembles that of Evx2 in limb and genital buds. After 10 dpc, however, Evx2 begins to be expressed in CNS as well. We analyzed the region responsible for these differences using ES cell techniques, and found that the intergenic region between Evx2 and Hoxd13 behaves as a boundary element that functions differentially in space and time, specifically in the development of limbs, genital bud, and brain. This boundary element comprises a large sequence spanning several kilobases that can be divided into at least two units: a constitutive boundary element, which blocks transcription regulatory influences from the chromosomal environment, and a regulatory element, which controls the function of the constitutive boundary element in time and space.", "link"=>"http://www.mendeley.com/research/evx2hoxd13-intergenic-region-restricts-enhancer-association-hoxd13-promoter", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Japan"=>1, "France"=>1, "Switzerland"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/953212"], "description"=>"<p>Genomic structure and expression patterns of <i>Evx2-Hoxd13.</i> (A) <i>Evx2</i> and <i>Hoxd13</i> genes are located within 8 kb of each other. (B) Expression patterns of <i>Evx2</i> (left panel) and <i>Hoxd13</i> (right panel) in 11 dpc embryos. <i>Evx2</i> is expressed in the CNS, as well as in the limbs and genital buds, regions that also express <i>Hoxd13.</i> (c) Scheme illustrating the hypothesis that <i>Evx2</i> and <i>Hoxd13</i> display segregated expression patterns. Enhancers located 3′ from <i>Evx2</i> have differential access to the <i>Evx2</i> promoter and the <i>Hoxd13</i> promoter. The intergenic region of <i>Evx2</i>-<i>Hoxd13</i> prevents enhancer access in CNS but not in limbs.</p>", "links"=>[], "tags"=>["developmental biology", "genetics and genomics", "molecular biology", "biotechnology/applied microbiology"], "article_id"=>623517, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000175.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_1_/623517", "title"=>"Figure 1", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:50:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/468810", "https://ndownloader.figshare.com/files/468884", "https://ndownloader.figshare.com/files/468954", "https://ndownloader.figshare.com/files/469014"], "description"=>"<div><p>Expression of <em>Hox</em> genes is tightly regulated in spatial and temporal domains. <em>Evx2</em> is located next to <em>Hoxd13</em> within 8 kb on the opposite DNA strand. Early in development, the pattern of <em>Hoxd13</em> expression resembles that of <em>Evx2</em> in limb and genital buds. After 10 dpc, however, <em>Evx2</em> begins to be expressed in CNS as well. We analyzed the region responsible for these differences using ES cell techniques, and found that the intergenic region between <em>Evx2</em> and <em>Hoxd13</em> behaves as a boundary element that functions differentially in space and time, specifically in the development of limbs, genital bud, and brain. This boundary element comprises a large sequence spanning several kilobases that can be divided into at least two units: a constitutive boundary element, which blocks transcription regulatory influences from the chromosomal environment, and a regulatory element, which controls the function of the constitutive boundary element in time and space.</p> </div>", "links"=>[], "tags"=>["intergenic", "restricts", "enhancer", "promoter"], "article_id"=>152437, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0000175.s001", "https://dx.doi.org/10.1371/journal.pone.0000175.s002", "https://dx.doi.org/10.1371/journal.pone.0000175.s003", "https://dx.doi.org/10.1371/journal.pone.0000175.s004"], "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/___Evx2_Hoxd13_Intergenic_Region_Restricts_Enhancer_Association_to_Hoxd13_Promoter/152437", "title"=>"<em>Evx2</em>-<em>Hoxd13</em> Intergenic Region Restricts Enhancer Association to <em>Hoxd13</em> Promoter", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-01-24 00:40:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/953684"], "description"=>"<p>Position-effect blocker activity of the XB fragment. (A) Constructs introduced into the NIH3T3 cell line. Construct I (top) contains a CAGGS promoter-driven fluorescent protein (Venus) and a neomycin-resistance gene, enabling G418 selection of stable transformant colonies of transfected NIH3T3 cells. Construct II (bottom) is organized similarly, except it contains XB blocker fragments bordering both sides of the Venus expression marker gene. (B) Experimental scheme illustrating the transfection scenario. Stable transformants of both constructs were selected using G418. Colonies were maintained in culture for one year. We selected samples from each colony after 1, 6, and 12 months for FACS analyses. (C) Fluorescence assessment of 12 colonies harboring either Construct I or Construct II. Fewer fluorescent cells were observed in colonies lacking the XB fragment, while numerous fluorescent cells were observed in colonies harboring the XB fragment, indicating that the XB construct (Construct II) maintained Venus expression.</p>", "links"=>[], "tags"=>["developmental biology", "genetics and genomics", "molecular biology", "biotechnology/applied microbiology"], "article_id"=>623988, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000175.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_6_/623988", "title"=>"Figure 6", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:53:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/953626"], "description"=>"<p>Premature expression of <i>Hoxd13</i> observed in XB-targeted transgenic mice. (A) <i>Hoxd13</i> expression in 7 dpc embryos was specifically upregulated. Sample RNA levels were normalized according to β-actin mRNA levels. W1–W3, samples from three litters arising from wild-type mice; B1–B6, samples from six litters arising from internally bred BB-transgenic mice; X1–X8, samples from eight litters arising from internally bred XB-transgenic mice. (B) Hypothetical scheme for premature expression of these genes in XB-transgenic mice. The region downstream of <i>Evx2</i> recruits repression over the <i>Hox</i> complex before the 7-dpc embryonic stage in preparation for <i>Hox</i> expression in wild-type and BB-targeted transgenic mice. The XB fragment disrupts repression, preventing the repressor region downstream of <i>Evx2</i> from recruiting repression into the <i>HoxD</i> complex.</p>", "links"=>[], "tags"=>["developmental biology", "genetics and genomics", "molecular biology", "biotechnology/applied microbiology"], "article_id"=>623933, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000175.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_5_/623933", "title"=>"Figure 5", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:53:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/953498"], "description"=>"<p>Insulation activity is spatially dependent. (A) Design of two targeted transgenic mice. XNs and XB as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000175#pone-0000175-g002\" target=\"_blank\">Figure 2A</a>. (B) Expression pattern of XNs- and XB-transgenic mouse embryos. XNs 11 dpc embryos expressed lacZ in the limbs and genital bud, whereas XB embryos did not. Limbs are shown in the boxed areas and genital buds are shown in the middle panels. (C) Scheme illustrating the regulation underlying enhancer-promoter interaction. Within the CNS, the XB fragment prevents interaction between the enhancer and <i>Hoxd13</i> promoter, while the BB fragment blocks the insulator activity of the XB fragment within the limbs and genital bud.</p>", "links"=>[], "tags"=>["developmental biology", "genetics and genomics", "molecular biology", "biotechnology/applied microbiology"], "article_id"=>623804, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000175.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_3_/623804", "title"=>"Figure 3", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:52:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/953566"], "description"=>"<p>Methylation profile of insulator fragment. (A) Hindbrain and forelimbs were dissected from 11 dpc embryos to obtain the DNA used for the methylation assays. (B) Map of the tested fragment. Red line represents the insulator (XB fragment) and blue line represents the regulator (BB fragment). Bisulfite-treated genomic DNA was subjected to PCR using three sets of primers (indicated by arrows; see Experimental Procedures). Primer pairs for one PCR reaction have matching arrow color. (C) Ten clones from each PCR product were sequenced. Their methylation status is shown here. White circles represent methylated cytosine residues, while black circles represent non-methylated cytosine residues.</p>", "links"=>[], "tags"=>["developmental biology", "genetics and genomics", "molecular biology", "biotechnology/applied microbiology"], "article_id"=>623876, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000175.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_4_/623876", "title"=>"Figure 4", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:53:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/953405"], "description"=>"<p>Analysis of the insulator fragment using targeted transgene experiments. (A) Scheme of experimental design. The <i>Hoxd9</i>/lacZ transgene, along with an insulator candidate fragment, was inserted into the region just downstream of <i>Evx2</i> by a gene-targeting technique using ES cells. The resulting ES cells were injected into blastocysts to establish transgenic mice. (B) The <i>Xho</i>I-<i>Nsi</i>I (XNs) fragment (red) was separated into three fragments—<i>Bam</i>HI-<i>Bam</i>HI (BB), <i>Eco</i>RI-<i>Bgl</i>II (EBg), and <i>Xho</i>I-<i>Bam</i>HI (XB)—each of which were translocated together with the <i>Hoxd9</i>/lacZ reporter transgene. (C–H) LacZ-stained 11 dpc embryos. XNs (C) and XB (F) blocked lacZ gene expression in brain, while BB (D) and EBg (E) failed to do so. Based on these results, we divided the XB fragment into two fragments—<i>Xho</i>I-<i>Eco</i>RI (XE) and <i>Eco</i>RI-<i>Eco</i>RI (EE)—which we used to make targeted transgenic mice having a similar configuration to that shown in panel (A). Embryos harboring XE (G) and EE (H) displayed lacZ gene expression in brain but did not display expression patterns indicative of insulation activity.</p>", "links"=>[], "tags"=>["developmental biology", "genetics and genomics", "molecular biology", "biotechnology/applied microbiology"], "article_id"=>623711, "categories"=>["Biotechnology", "Molecular Biology", "Genetics", "Developmental Biology"], "users"=>["Takumi Yamagishi", "Michiru Ozawa", "Chiho Ohtsuka", "Ritsuko Ohyama-Goto", "Takashi Kondo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000175.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Figure_2_/623711", "title"=>"Figure 2", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 12:51:53"}

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Relative Metric

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