Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates
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{"title"=>"Molecular cloning, functional characterization, and evolutionary analysis of vitamin D receptors isolated from basal vertebrates", "type"=>"journal", "authors"=>[{"first_name"=>"Erin M.", "last_name"=>"Kollitz", "scopus_author_id"=>"35848677700"}, {"first_name"=>"Guozhu", "last_name"=>"Zhang", "scopus_author_id"=>"56647110800"}, {"first_name"=>"Mary Beth", "last_name"=>"Hawkins", "scopus_author_id"=>"7202429134"}, {"first_name"=>"G. Kerr", "last_name"=>"Whitfield", "scopus_author_id"=>"7005389357"}, {"first_name"=>"David M.", "last_name"=>"Reif", "scopus_author_id"=>"9274088800"}, {"first_name"=>"Seth W.", "last_name"=>"Kullman", "scopus_author_id"=>"6603845366"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"604107770", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0122853", "scopus"=>"2-s2.0-84929469049", "pmid"=>"25855982", "sgr"=>"84929469049"}, "id"=>"2799a89e-ba3e-35c4-be47-ab7101a106aa", "abstract"=>"The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been driven by changes in protein-protein interactions between VDR and essential coregulators.", "link"=>"http://www.mendeley.com/research/molecular-cloning-functional-characterization-evolutionary-analysis-vitamin-d-receptors-isolated-bas", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>9}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2012337", "https://ndownloader.figshare.com/files/2012338", "https://ndownloader.figshare.com/files/2012339"], "description"=>"<div><p>The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (<i>Petromyzon marinus</i>), a 1R jawless fish; the little skate (<i>Leucoraja erinacea</i>), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (<i>Polypterus senegalus</i>), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC<sub>50</sub> values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D<sub>3</sub> acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D<sub>3</sub> throughout vertebrate evolution that may have been driven by changes in protein-protein interactions between VDR and essential coregulators.</p></div>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373246, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0122853.s001", "https://dx.doi.org/10.1371/journal.pone.0122853.s002", "https://dx.doi.org/10.1371/journal.pone.0122853.s003"], "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_Cloning_Functional_Characterization_and_Evolutionary_Analysis_of_Vitamin_D_Receptors_Isolated_from_Basal_Vertebrates_/1373246", "title"=>"Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012326"], "description"=>"<p>The numbers in the table correspond to percent sequence identity.</p><p>Key: Lamprey (L), Skate (S), Elephant Shark (ES), Bichir (B), Zebrafish α (ZFα), Zebrafish β (ZFβ), Medaka α (Mα), Medaka β (Mβ), Frog (F), Alligator (A), Chicken (C), Rat (R), Human (H).</p><p>Homology of full-length vertebrate VDRs.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373243, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Homology_of_full_length_vertebrate_VDRs_/1373243", "title"=>"Homology of full-length vertebrate VDRs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012311"], "description"=>"<p>Functional domains and domain elements were determined based on previous work with human VDR discussed in the manuscript. Fully conserved residues are indicated by “*”. Partial conservation is indicated by “:” (strong) or “.” (weak). Lack of residue consensus is indicated by a blank space. The five functional domains are shaded as follows: The N-terminal A/B domain and the C-terminal F domain are shaded in olive green. The DNA binding domain (DBD) is shaded in orange. The CTE/hinge domain is shaded in purple, while the ligand binding domain (LBD) is shaded in blue. For the DBD, residues that make up the P-box and D-box are indicated with a solid black line, and helix 1 (the recognition helix) and helix 2 are highlighted in yellow. Conserved cysteine residues involved in zinc finger structure are both bold and blue. For the CTE/hinge domain, the T-box and A-box are indicated with solid black lines. For the LBD, the estimated α-helices are highlighted in yellow and identified with the letter H followed by the helix number. The three β-sheets are highlighted in bright green. Amino acid residues that serve as contacts for 1, 25D<sub>3</sub> are bold and red. The K and E residues in H3 and H12 involved in the charge clamp formation bold, white, and highlighted in black. A red circle above a residue indicates that the residue plays a role in direct interaction with other VDR residues upon ligand binding.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373228, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amino_acid_sequence_alignment_of_lamprey_skate_bichir_and_human_VDRs_/1373228", "title"=>"Amino acid sequence alignment of lamprey, skate, bichir, and human VDRs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012325"], "description"=>"<p>The numbers in the table correspond to percent sequence identity.</p><p>Key: Lamprey (L), Skate (S), Elephant Shark (ES), Bichir (B), Zebrafish α (ZFα), Zebrafish β (ZFβ), Medaka α (Mα), Medaka β (Mβ), Frog (F), Alligator (A), Chicken (C), Rat (R), Human (H).</p><p>Homology of vertebrate VDR ligand-binding domains (LBDs).</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373242, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.t002", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Homology_of_vertebrate_VDR_ligand_binding_domains_LBDs_/1373242", "title"=>"Homology of vertebrate VDR ligand-binding domains (LBDs).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012320"], "description"=>"<p>(A) Analysis of overexpressed RXR on VDR transactivation and (B) VDR-RXR heterodimerization in response to 1, 25D<sub>3</sub>. (A) HepG2 cells were transiently transfected with pSG5-VDR, the XREM-Luc reporter, and the pRL-CMV internal luciferase control as described previously in Materials and Methods. Select assays were cotransfected with pCDNA-RXR<sub>WT</sub> (orange bars) or pCDNA-RXR<sub>AF2</sub> mutant (blue bars). Cells were treated with 120 nM 1, 25D<sub>3</sub> for 24 hours. VDR response was measured via dual-luciferase assays. Data are represented as the average fold activation normalized to VDR alone (no RXR) ± SEM (n = 4). Asterisks represent a significant increase in transactivation compared to the VDR control: *** = p < 0.001, ** = p < 0.01, * = p < 0.05. (B) Mammalian two-hybrid assays were conducted to study VDR-RXR heterodimerization in response to 1, 25D<sub>3</sub>. HepG2 cells were transiently transfected with pVP16-VDR as prey and pM-RXR<sub>WT</sub> (light orange bars) or pM-RXR<sub>AF2</sub> (light blue bars) as bait, along with the Gal4 luciferase reporter 5XGal4-TATA-Luc and the pRL-CMV internal luciferase control. Select experiments were also cotransfected with pSG5-SRC1 where indicated. Cells were exposed to 120 nM 1, 25D<sub>3</sub> in media for 24 hours. Protein-protein interaction was measured via dual-luciferase assays as described in the Materials and Methods. Data are represented as the mean fold interaction ± SEM (n = 4). Data are normalized to VDR + empty pM vector (no RXR). Asterisks indicate significance: *** = p < 0.001, ** = p < 0.01, * = p < 0.05. Asterisks above brackets indicate the addition of pSG5-SRC1 significantly enhanced VDR-RXR interaction.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373237, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g006", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Assessment_of_VDR_RXR_interactions_/1373237", "title"=>"Assessment of VDR-RXR interactions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012319"], "description"=>"<p>The above images depict VDR-RXR heterodimer binding to both (A) the canonical VDRE, and (B) the VDRE from the XREM region of CYP3A4. (A) With the canonical VDRE, DNA binding complexes were only observed in the presence of RXR<sub>WT</sub> (lanes 2, 4, 6, 8 vs. lanes 1, 3, 5, 7). The addition of 100 nM 1, 25D<sub>3</sub> (lanes 5–8) visibly enhanced binding complex formation compared to the ethanol control (lanes 1–4). In competition assays, the addition of 100-fold molar excess of the unlabeled wild type competitor (VDRE<sub>WT</sub>) successfully outcompeted binding to the labeled VDRE (lanes 2 vs. 3 and 6 vs. 7). The use of the mutant competitor (VDRE<sub>MUT</sub>) did not inhibit complex formation with any VDR tested (lanes 2 vs. 4 and 6 vs. 8). (B) A similar pattern was observed with the XREM VDRE. Complex formation was only observed in the presence of recombinant RXR<sub>WT</sub> (lanes 1 vs. 2 and 4 vs. 5). The addition of 100 nM 1, 25D<sub>3</sub> visibly enhanced complex formation (lane 2 vs. lane 5). In competition assays, the addition of 100-fold molar excess of the unlabeled XREM VDRE<sub>WT</sub> successfully outcompeted complex formation on the labeled XREM VDRE (lanes 2 vs. 3 and 5 vs. 6).</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373236, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g005", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electrophoretic_mobility_shift_analysis_of_recombinant_lamprey_skate_bichir_and_human_VDR_/1373236", "title"=>"Electrophoretic mobility shift analysis of recombinant lamprey, skate, bichir, and human VDR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012316"], "description"=>"<p>Phylogenetic analysis was conducted in MEGA 5. This tree was estimated using the Maximum Likelihood method based on the JTT matrix-based model. The analysis was bootstrapped (500 pseudosamples) to assess robustness. The percentage of replicate trees in which the associated taxa cluster together in the bootstrap tests is illustrated at each node. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The locations of each WGD (1R, 2R, and 3R) in vertebrate evolution are indicated on the tree and by branch color: green for 1R, blue for 2R, and red for 3R. The GenBank accession numbers for each VDR can be found in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122853#pone.0122853.s002\" target=\"_blank\">S2 Table</a>.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373233, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g002", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogenetic_analysis_of_full_length_VDR_amino_acid_sequences_in_vertebrates_/1373233", "title"=>"Phylogenetic analysis of full-length VDR amino acid sequences in vertebrates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012324"], "description"=>"<p>The numbers in the table correspond to percent sequence identity.</p><p>Key: Lamprey (L), Skate (S), Elephant Shark (ES), Bichir (B), Zebrafish α (ZFα), Zebrafish β (ZFβ), Medaka α (Mα), Medaka β (Mβ), Frog (F), Alligator (A), Chicken (C), Rat (R), Human (H).</p><p>Homology of vertebrate VDR DNA-binding domains (DBDs).</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373241, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.t001", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Homology_of_vertebrate_VDR_DNA_binding_domains_DBDs_/1373241", "title"=>"Homology of vertebrate VDR DNA-binding domains (DBDs).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012322"], "description"=>"<p>The above graphs depict (A) lamprey VDR, (B) skate VDR, (C) bichir VDR, and (D) human VDR. Assays were conducted both in the presence (+) and absence (-) of pCDNA-RXR<sub>WT</sub>. HepG2 cells were transiently transfected with pVP16-VDR as prey and pM-SRC1 (orange bars), pM-GRIP1 (blue bars), or pM-ACTR (yellow bars) as bait, along with the 5XGal4-TATA-Luc reporter and pRL-CMV as an internal luciferase control. Cells were exposed to 120 nM 1, 25D<sub>3</sub> in media for 24 hours. Protein-protein interaction was measured via dual-luciferase assays as described in the Materials and Methods. Data are represented as the mean fold interaction ± SEM (n = 4). Data are normalized to VDR + empty pM vector (no coactivators). Asterisks above bars represent a significant interaction between VDR and the SRC/p160 coactivators: *** = p < 0.001, ** = p < 0.01, * = p < 0.05. Asterisks above brackets indicate the addition of RXR<sub>WT</sub> significantly enhanced VDR-SRC/p160 interaction. The interaction between pVP16-skate VDR and pM-SRC1 was tested with an unpaired t-test: t<sub>6</sub> = 16.56, p < 0.0001 (†).</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373239, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g008", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mammalian_2_hybrid_analysis_of_VDR_interaction_with_SRC_p160_coactivators_in_response_to_1_25D_3_/1373239", "title"=>"Mammalian 2-hybrid analysis of VDR interaction with SRC/p160 coactivators in response to 1, 25D<sub>3</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012323"], "description"=>"<p>(A) Clustering includes eight VDR orthologs with Manhattan distance and complete linkage. Data for each assay (rows) were standardized as z-scores across all eight VDR species (columns) to account for interspecies differences in absolute assay readout. (B) The Pickett Plot to the right of the heatmap indicates the presence/absence of coregulators within each assay.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373240, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g009", "stats"=>{"downloads"=>0, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_clustering_of_transient_transactivation_TT_and_mammalian_2_hybrid_M2H_assays_/1373240", "title"=>"Hierarchical clustering of transient transactivation (TT) and mammalian 2-hybrid (M2H) assays.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012321"], "description"=>"<p>The above graphs depict (A) lamprey VDR, (B) skate VDR, (C) bichir VDR, and (D) human VDR. HepG2 cells were transiently transfected with pSG5-VDR, the XREM-Luc reporter, and the pRL-CMV internal luciferase control as described previously in Materials and Methods. Select assays were cotransfected with pSG5-SRC1 (orange bars), pSG5-GRIP1 (blue bars), pSG5-ACTR (yellow bars), or no SRC/p160 coactivators (black bars). Assays were conducted both in the presence (+) and absence (-) of pCDNA-RXR<sub>WT</sub>. Cells were treated with 120 nM 1, 25D<sub>3</sub> for 24 hours. VDR response was measured via dual-luciferase assays as described. Data are represented as the average fold activation normalized to VDR alone ± SEM (n = 4). Asterisks indicate significance: *** = p < 0.001, ** = p < 0.01, * = p < 0.05. Asterisks above brackets indicate the combination of RXR<sub>WT</sub> the indicated SRC/p160 coactivator significantly increased VDR transactivation compared to the SRC/p160 coactivator in the absence of RXR<sub>WT</sub>. The letter “b” indicates the combination of both RXR<sub>WT</sub> and the indicated SRC/p160 coactivator had a greater effect on VDR transactivation compared with VDR + RXR<sub>WT</sub> in the absence of the SRC/p160 coactivator (black bar). The letter “a” indicates that no difference in VDR transactivation was observed in the presence of both RXR<sub>WT</sub> and the indicated SRC/p160 coactivator vs. VDR + RXR<sub>WT</sub> in the absence of the SRC/p160 coactivator. (p < 0.05).</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373238, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g007", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Influence_of_overexpressed_SRC_p160_coactivators_on_VDR_transactivation_in_response_to_1_25D_3_/1373238", "title"=>"Influence of overexpressed SRC/p160 coactivators on VDR transactivation in response to 1, 25D<sub>3</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012318"], "description"=>"<p>Saturation binding profiles are shown for lamprey VDR (red), skate VDR (orange), bichir VDR (green), and human VDR (blue). Lysates were prepared from transfected Cos7 cells as described in Materials and Methods. Lysates were incubated with 0–1.6 nM [<sup>3</sup>H]-1, 25D<sub>3</sub> for 18 hours at 4°C. Unbound ligand was removed as described. Specific binding values were calculated by subtracting the average non-specific binding counts from the total binding counts. Hyperbolic one-site binding curves were fit using Prism 4. The reported dissociation constant (K<sub>d</sub>) in the manuscript for each VDR is the average of three or four separate experiments ± SEM. The graphs shown here are specific binding data from a representative experiment.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373235, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Saturation_binding_analysis_of_lamprey_skate_bichir_and_human_VDR_to_3_H_1_25D_3_/1373235", "title"=>"Saturation binding analysis of lamprey, skate, bichir, and human VDR to [<sup>3</sup>H]-1, 25D<sub>3</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/2012317"], "description"=>"<p>Concentration-response profiles are shown for lamprey VDR (red), skate VDR (orange), bichir VDR (green), and human VDR (blue). HepG2 cells were transiently transfected with full-length pSG5-VDR, the XREM-Luc reporter, and the pRL-CMV internal luciferase control as described previously in Materials and Methods. Cells were treated with 0–1200 nM 1, 25D<sub>3</sub> in media for 24 hours. VDR response was measured via dual-luciferase assays. Data are represented as the mean fold activation normalized to the ethanol control ± SEM (n = 4). The half-maximal effective concentration (EC<sub>50</sub>), 95% confidence interval (95% CI), and maximum efficacy (E<sub>MAX</sub>) values for each VDR was determined using nonlinear regression analysis using a sigmoidal dose-response calculation with variable slope in Prism 4.</p>", "links"=>[], "tags"=>["bioinformatics analysis", "3 R teleosts", "Vitamin D Receptors", "EC 50 values", "DNA binding characteristics", "evolution", "1 R jawless fish", "Concentration response curves", "vdr", "2 R event", "interaction", "basal species", "affinity ligand binding", "coregulator activation domains", "3 R event", "paralog", "Saturation binding assays", "genome", "gel mobility shift assays"], "article_id"=>1373234, "categories"=>["Uncategorised"], "users"=>["Erin M. Kollitz", "Guozhu Zhang", "Mary Beth Hawkins", "G. Kerr Whitfield", "David M. Reif", "Seth W. Kullman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122853.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transactivation_of_lamprey_skate_bichir_and_human_VDR_in_response_to_1_25D_3_/1373234", "title"=>"Transactivation of lamprey, skate, bichir, and human VDR in response to 1, 25D<sub>3</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-09 03:46:29"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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