AustralieFrV1, Main, Exploration, bibRecord, 003188

Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.

Identifieur interne : 003188 ( Main/Exploration ); précédent : 003187; suivant : 003189

Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.

Auteurs : Jonathan Lefebvre [France] ; Michael Clarkson [France] ; Filippo Massa [France] ; Stephen T. Bradford [Australie] ; Aurelie Charlet [France] ; Fabian Buske [Australie] ; Sandra Lacas-Gervais [France] ; Herbert Schulz [Allemagne] ; Charlotte Gimpel [Allemagne] ; Yutaka Hata [Japon] ; Franz Schaefer [Allemagne] ; Andreas Schedl [France]

Source :

Kidney international [ 1523-1755 ] ; 2015.

RBID : pubmed:25993318

Descripteurs français

English descriptors

KwdEn :
- Adaptor Proteins, Signal Transducing (genetics), Adaptor Proteins, Signal Transducing (metabolism), Alternative Splicing, Animals, Binding Sites, Cell Differentiation (genetics), Down-Regulation (drug effects), Exons, Female, Forkhead Transcription Factors (genetics), Glomerulonephritis, Membranoproliferative (metabolism), Glomerulosclerosis, Focal Segmental (metabolism), Guanylate Kinases (genetics), Guanylate Kinases (metabolism), Humans, Lipopolysaccharides (pharmacology), Membrane Proteins (metabolism), Mice, Mutation, Oligonucleotide Array Sequence Analysis, Podocytes (pathology), Podocytes (physiology), Promoter Regions, Genetic, Protein Isoforms (genetics), Repressor Proteins (genetics), Repressor Proteins (metabolism), Transcription, Genetic.
MESH :
- chemical , genetics : Adaptor Proteins, Signal Transducing, Forkhead Transcription Factors, Guanylate Kinases, Protein Isoforms, Repressor Proteins.
- chemical , metabolism : Adaptor Proteins, Signal Transducing, Guanylate Kinases, Membrane Proteins, Repressor Proteins.
- drug effects : Down-Regulation.
- genetics : Cell Differentiation.
- metabolism : Glomerulonephritis, Membranoproliferative, Glomerulosclerosis, Focal Segmental.
- pathology : Podocytes.
- chemical , pharmacology : Lipopolysaccharides.
- physiology : Podocytes.
- Alternative Splicing, Animals, Binding Sites, Exons, Female, Humans, Mice, Mutation, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Transcription, Genetic.

Abstract

The Wilms' tumor suppressor WT1 is a key regulator of podocyte function that is mutated in Denys-Drash and Frasier syndromes. Here we have used an integrative approach employing ChIP, exon array, and genetic analyses in mice to address general and isoform-specific functions of WT1 in podocyte differentiation. Analysis of ChIP-Seq data showed that almost half of the podocyte-specific genes are direct targets of WT1. Bioinformatic analysis further identified coactivator FOXC1-binding sites in proximity to WT1-bound regions, thus supporting coordinated action of these transcription factors in regulating podocyte-specific genes. Transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) had a more restrictive set of genes whose expression depends on these alternatively spliced isoforms. One of these genes encodes the membrane-associated guanylate kinase MAGI2, a protein that localizes to the base of the slit diaphragm. Using functional analysis in mice, we further show that MAGI2α is essential for proper localization of nephrin and the assembly of the slit diaphragm complex. Finally, a dramatic reduction of MAGI2 was found in an LPS mouse model of glomerular injury and in genetic cases of human disease. Thus, our study highlights the central role of WT1 in podocyte differentiation, identifies that WT1 has a central role in podocyte differentiation, and identifies MAGI2α as the crucial isoform in slit diaphragm assembly, suggesting a causative role of this gene in the etiology of glomerular disorders.

DOI: 10.1038/ki.2015.140
PubMed: 25993318

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.</title>
<author><name sortKey="Lefebvre, Jonathan" sort="Lefebvre, Jonathan" uniqKey="Lefebvre J" first="Jonathan" last="Lefebvre">Jonathan Lefebvre</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Clarkson, Michael" sort="Clarkson, Michael" uniqKey="Clarkson M" first="Michael" last="Clarkson">Michael Clarkson</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Massa, Filippo" sort="Massa, Filippo" uniqKey="Massa F" first="Filippo" last="Massa">Filippo Massa</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bradford, Stephen T" sort="Bradford, Stephen T" uniqKey="Bradford S" first="Stephen T" last="Bradford">Stephen T. Bradford</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France [4] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [5] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France [4] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [5] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Charlet, Aurelie" sort="Charlet, Aurelie" uniqKey="Charlet A" first="Aurelie" last="Charlet">Aurelie Charlet</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Buske, Fabian" sort="Buske, Fabian" uniqKey="Buske F" first="Fabian" last="Buske">Fabian Buske</name>
<affiliation wicri:level="1"><nlm:affiliation>1] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [2] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>1] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [2] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lacas Gervais, Sandra" sort="Lacas Gervais, Sandra" uniqKey="Lacas Gervais S" first="Sandra" last="Lacas-Gervais">Sandra Lacas-Gervais</name>
<affiliation wicri:level="3"><nlm:affiliation>CCMA University of Nice, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CCMA University of Nice, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schulz, Herbert" sort="Schulz, Herbert" uniqKey="Schulz H" first="Herbert" last="Schulz">Herbert Schulz</name>
<affiliation wicri:level="3"><nlm:affiliation>MDC for Molecular Medicine, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>MDC for Molecular Medicine, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gimpel, Charlotte" sort="Gimpel, Charlotte" uniqKey="Gimpel C" first="Charlotte" last="Gimpel">Charlotte Gimpel</name>
<affiliation wicri:level="3"><nlm:affiliation>University Children's Hospital, Freiburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University Children's Hospital, Freiburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hata, Yutaka" sort="Hata, Yutaka" uniqKey="Hata Y" first="Yutaka" last="Hata">Yutaka Hata</name>
<affiliation wicri:level="3"><nlm:affiliation>Tokyo Medical and Dental University, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Tokyo Medical and Dental University, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schaefer, Franz" sort="Schaefer, Franz" uniqKey="Schaefer F" first="Franz" last="Schaefer">Franz Schaefer</name>
<affiliation wicri:level="3"><nlm:affiliation>University Children's Hospital, Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University Children's Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schedl, Andreas" sort="Schedl, Andreas" uniqKey="Schedl A" first="Andreas" last="Schedl">Andreas Schedl</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2015">2015</date>
<idno type="RBID">pubmed:25993318</idno>
<idno type="pmid">25993318</idno>
<idno type="doi">10.1038/ki.2015.140</idno>
<idno type="wicri:Area/PubMed/Corpus">002B14</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002B14</idno>
<idno type="wicri:Area/PubMed/Curation">002A43</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002A43</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002A43</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002A43</idno>
<idno type="wicri:Area/Ncbi/Merge">002594</idno>
<idno type="wicri:Area/Ncbi/Curation">002594</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002594</idno>
<idno type="wicri:Area/Main/Merge">003189</idno>
<idno type="wicri:Area/Main/Curation">003188</idno>
<idno type="wicri:Area/Main/Exploration">003188</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.</title>
<author><name sortKey="Lefebvre, Jonathan" sort="Lefebvre, Jonathan" uniqKey="Lefebvre J" first="Jonathan" last="Lefebvre">Jonathan Lefebvre</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Clarkson, Michael" sort="Clarkson, Michael" uniqKey="Clarkson M" first="Michael" last="Clarkson">Michael Clarkson</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Massa, Filippo" sort="Massa, Filippo" uniqKey="Massa F" first="Filippo" last="Massa">Filippo Massa</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bradford, Stephen T" sort="Bradford, Stephen T" uniqKey="Bradford S" first="Stephen T" last="Bradford">Stephen T. Bradford</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France [4] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [5] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France [4] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [5] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Charlet, Aurelie" sort="Charlet, Aurelie" uniqKey="Charlet A" first="Aurelie" last="Charlet">Aurelie Charlet</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Buske, Fabian" sort="Buske, Fabian" uniqKey="Buske F" first="Fabian" last="Buske">Fabian Buske</name>
<affiliation wicri:level="1"><nlm:affiliation>1] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [2] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>1] CSIRO Food and Nutrition Flagship, North Ryde, New South Wales, Australia [2] Epigenetics Group, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lacas Gervais, Sandra" sort="Lacas Gervais, Sandra" uniqKey="Lacas Gervais S" first="Sandra" last="Lacas-Gervais">Sandra Lacas-Gervais</name>
<affiliation wicri:level="3"><nlm:affiliation>CCMA University of Nice, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>CCMA University of Nice, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schulz, Herbert" sort="Schulz, Herbert" uniqKey="Schulz H" first="Herbert" last="Schulz">Herbert Schulz</name>
<affiliation wicri:level="3"><nlm:affiliation>MDC for Molecular Medicine, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>MDC for Molecular Medicine, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gimpel, Charlotte" sort="Gimpel, Charlotte" uniqKey="Gimpel C" first="Charlotte" last="Gimpel">Charlotte Gimpel</name>
<affiliation wicri:level="3"><nlm:affiliation>University Children's Hospital, Freiburg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University Children's Hospital, Freiburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hata, Yutaka" sort="Hata, Yutaka" uniqKey="Hata Y" first="Yutaka" last="Hata">Yutaka Hata</name>
<affiliation wicri:level="3"><nlm:affiliation>Tokyo Medical and Dental University, Tokyo, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Tokyo Medical and Dental University, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schaefer, Franz" sort="Schaefer, Franz" uniqKey="Schaefer F" first="Franz" last="Schaefer">Franz Schaefer</name>
<affiliation wicri:level="3"><nlm:affiliation>University Children's Hospital, Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University Children's Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schedl, Andreas" sort="Schedl, Andreas" uniqKey="Schedl A" first="Andreas" last="Schedl">Andreas Schedl</name>
<affiliation wicri:level="3"><nlm:affiliation>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institute of Biology Valrose, Université de Nice-Sophia, Nice, France [2] Inserm, UMR1091, Nice, France [3] CNRS, UMR7277, Nice</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
<region type="old region">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Nice</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Kidney international</title>
<idno type="eISSN">1523-1755</idno>
<imprint><date when="2015" type="published">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Signal Transducing (genetics)</term>
<term>Adaptor Proteins, Signal Transducing (metabolism)</term>
<term>Alternative Splicing</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Cell Differentiation (genetics)</term>
<term>Down-Regulation (drug effects)</term>
<term>Exons</term>
<term>Female</term>
<term>Forkhead Transcription Factors (genetics)</term>
<term>Glomerulonephritis, Membranoproliferative (metabolism)</term>
<term>Glomerulosclerosis, Focal Segmental (metabolism)</term>
<term>Guanylate Kinases (genetics)</term>
<term>Guanylate Kinases (metabolism)</term>
<term>Humans</term>
<term>Lipopolysaccharides (pharmacology)</term>
<term>Membrane Proteins (metabolism)</term>
<term>Mice</term>
<term>Mutation</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Podocytes (pathology)</term>
<term>Podocytes (physiology)</term>
<term>Promoter Regions, Genetic</term>
<term>Protein Isoforms (genetics)</term>
<term>Repressor Proteins (genetics)</term>
<term>Repressor Proteins (metabolism)</term>
<term>Transcription, Genetic</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Différenciation cellulaire (génétique)</term>
<term>Exons</term>
<term>Facteurs de transcription Forkhead (génétique)</term>
<term>Femelle</term>
<term>Glomérulonéphrite membranoproliférative (métabolisme)</term>
<term>Glomérulonéphrite segmentaire et focale (métabolisme)</term>
<term>Guanylate kinase (génétique)</term>
<term>Guanylate kinase (métabolisme)</term>
<term>Humains</term>
<term>Isoformes de protéines (génétique)</term>
<term>Lipopolysaccharides (pharmacologie)</term>
<term>Mutation</term>
<term>Podocytes (anatomopathologie)</term>
<term>Podocytes (physiologie)</term>
<term>Protéines adaptatrices de la transduction du signal (génétique)</term>
<term>Protéines adaptatrices de la transduction du signal (métabolisme)</term>
<term>Protéines de répression (génétique)</term>
<term>Protéines de répression (métabolisme)</term>
<term>Protéines membranaires (métabolisme)</term>
<term>Régions promotrices (génétique)</term>
<term>Régulation négative ()</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Transcription génétique</term>
<term>Épissage alternatif</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term>
<term>Forkhead Transcription Factors</term>
<term>Guanylate Kinases</term>
<term>Protein Isoforms</term>
<term>Repressor Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term>
<term>Guanylate Kinases</term>
<term>Membrane Proteins</term>
<term>Repressor Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Podocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Down-Regulation</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cell Differentiation</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Différenciation cellulaire</term>
<term>Facteurs de transcription Forkhead</term>
<term>Guanylate kinase</term>
<term>Isoformes de protéines</term>
<term>Protéines adaptatrices de la transduction du signal</term>
<term>Protéines de répression</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Glomerulonephritis, Membranoproliferative</term>
<term>Glomerulosclerosis, Focal Segmental</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glomérulonéphrite membranoproliférative</term>
<term>Glomérulonéphrite segmentaire et focale</term>
<term>Guanylate kinase</term>
<term>Protéines adaptatrices de la transduction du signal</term>
<term>Protéines de répression</term>
<term>Protéines membranaires</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Podocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Lipopolysaccharides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Lipopolysaccharides</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Podocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Podocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Alternative Splicing</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Exons</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mutation</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Promoter Regions, Genetic</term>
<term>Transcription, Genetic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Exons</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mutation</term>
<term>Régions promotrices (génétique)</term>
<term>Régulation négative</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Transcription génétique</term>
<term>Épissage alternatif</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The Wilms' tumor suppressor WT1 is a key regulator of podocyte function that is mutated in Denys-Drash and Frasier syndromes. Here we have used an integrative approach employing ChIP, exon array, and genetic analyses in mice to address general and isoform-specific functions of WT1 in podocyte differentiation. Analysis of ChIP-Seq data showed that almost half of the podocyte-specific genes are direct targets of WT1. Bioinformatic analysis further identified coactivator FOXC1-binding sites in proximity to WT1-bound regions, thus supporting coordinated action of these transcription factors in regulating podocyte-specific genes. Transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) had a more restrictive set of genes whose expression depends on these alternatively spliced isoforms. One of these genes encodes the membrane-associated guanylate kinase MAGI2, a protein that localizes to the base of the slit diaphragm. Using functional analysis in mice, we further show that MAGI2α is essential for proper localization of nephrin and the assembly of the slit diaphragm complex. Finally, a dramatic reduction of MAGI2 was found in an LPS mouse model of glomerular injury and in genetic cases of human disease. Thus, our study highlights the central role of WT1 in podocyte differentiation, identifies that WT1 has a central role in podocyte differentiation, and identifies MAGI2α as the crucial isoform in slit diaphragm assembly, suggesting a causative role of this gene in the etiology of glomerular disorders.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>Japon</li>
</country>
<region><li>Bade-Wurtemberg</li>
<li>Berlin</li>
<li>District de Fribourg-en-Brisgau</li>
<li>District de Karlsruhe</li>
<li>Provence-Alpes-Côte d'Azur</li>
<li>Région de Kantō</li>
</region>
<settlement><li>Berlin</li>
<li>Fribourg-en-Brisgau</li>
<li>Heidelberg</li>
<li>Nice</li>
<li>Tokyo</li>
</settlement>
</list>
<tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Lefebvre, Jonathan" sort="Lefebvre, Jonathan" uniqKey="Lefebvre J" first="Jonathan" last="Lefebvre">Jonathan Lefebvre</name>
</region>
<name sortKey="Charlet, Aurelie" sort="Charlet, Aurelie" uniqKey="Charlet A" first="Aurelie" last="Charlet">Aurelie Charlet</name>
<name sortKey="Clarkson, Michael" sort="Clarkson, Michael" uniqKey="Clarkson M" first="Michael" last="Clarkson">Michael Clarkson</name>
<name sortKey="Lacas Gervais, Sandra" sort="Lacas Gervais, Sandra" uniqKey="Lacas Gervais S" first="Sandra" last="Lacas-Gervais">Sandra Lacas-Gervais</name>
<name sortKey="Massa, Filippo" sort="Massa, Filippo" uniqKey="Massa F" first="Filippo" last="Massa">Filippo Massa</name>
<name sortKey="Schedl, Andreas" sort="Schedl, Andreas" uniqKey="Schedl A" first="Andreas" last="Schedl">Andreas Schedl</name>
</country>
<country name="Australie"><noRegion><name sortKey="Bradford, Stephen T" sort="Bradford, Stephen T" uniqKey="Bradford S" first="Stephen T" last="Bradford">Stephen T. Bradford</name>
</noRegion>
<name sortKey="Buske, Fabian" sort="Buske, Fabian" uniqKey="Buske F" first="Fabian" last="Buske">Fabian Buske</name>
</country>
<country name="Allemagne"><region name="Berlin"><name sortKey="Schulz, Herbert" sort="Schulz, Herbert" uniqKey="Schulz H" first="Herbert" last="Schulz">Herbert Schulz</name>
</region>
<name sortKey="Gimpel, Charlotte" sort="Gimpel, Charlotte" uniqKey="Gimpel C" first="Charlotte" last="Gimpel">Charlotte Gimpel</name>
<name sortKey="Schaefer, Franz" sort="Schaefer, Franz" uniqKey="Schaefer F" first="Franz" last="Schaefer">Franz Schaefer</name>
</country>
<country name="Japon"><region name="Région de Kantō"><name sortKey="Hata, Yutaka" sort="Hata, Yutaka" uniqKey="Hata Y" first="Yutaka" last="Hata">Yutaka Hata</name>
</region>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003188 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003188 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:25993318
   |texte=   Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:25993318" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Dec 5 10:43:12 2017. Site generation: Tue Mar 5 14:07:20 2024

Serveur d'exploration sur les relations entre la France et l'Australie

Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.

Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.