Identification of Novel Craniofacial Regulatory Domains Located far Upstream of SOX9 and Disrupted in Pierre Robin Sequence
Identifieur interne : 003D87 ( Main/Exploration ); précédent : 003D86; suivant : 003D88Identification of Novel Craniofacial Regulatory Domains Located far Upstream of SOX9 and Disrupted in Pierre Robin Sequence
Auteurs : Christopher T. Gordon [France] ; Catia Attanasio [États-Unis, Suisse] ; Shipra Bhatia [Royaume-Uni] ; Sabina Benko [France, États-Unis] ; Morad Ansari [Royaume-Uni] ; Tiong Y. Tan [Australie] ; Arnold Munnich [France] ; Len A. Pennacchio [États-Unis] ; Véronique Abadie [France] ; I. Karen Temple [Royaume-Uni] ; Alice Goldenberg [France] ; Veronica Van Heyningen [Royaume-Uni] ; Jeanne Amiel [France] ; David Fitzpatrick [Royaume-Uni] ; Dirk A. Kleinjan [Royaume-Uni] ; Axel Visel [États-Unis] ; Stanislas Lyonnet [France]Source :
- Human Mutation [ 1059-7794 ] ; 2014-08.
Abstract
Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions, and duplications within a ∼2 Mb region upstream of SOX9 can recapitulate the CD–DSD phenotype fully or partially, suggesting the existence of an unusually large cis‐regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ∼1.2–1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harboring candidate craniofacial regulatory elements. In parallel, ChIP‐Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple noncoding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS.
Url:
- https://api.istex.fr/document/4B65229FDA86C14B5421D0AC7CAEB415D7BAB56F/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389788
DOI: 10.1002/humu.22606
Affiliations:
- Australie, France, Royaume-Uni, Suisse, États-Unis
- Californie, Canton de Vaud, Haute-Normandie, Région Normandie, Victoria (État), Écosse, État de New York, Île-de-France
- Lausanne, Melbourne, New York, Paris, Rouen, Édimbourg
- Université Paris-Descartes, Université d'Édimbourg
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Le document en format XML
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Pennacchio</name><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Genomics Division, Lawrence Berkeley National Laboratory, Berkeley</wicri:cityArea></affiliation><affiliation><wicri:noCountry code="subField">Creek</wicri:noCountry></affiliation></author><author><name sortKey="Abadie, Veronique" sort="Abadie, Veronique" uniqKey="Abadie V" first="Véronique" last="Abadie">Véronique Abadie</name><affiliation wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker‐Enfants Malades, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Temple, I Karen" sort="Temple, I Karen" uniqKey="Temple I" first="I. Karen" last="Temple">I. Karen Temple</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton</wicri:regionArea><wicri:noRegion>Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Goldenberg, Alice" sort="Goldenberg, Alice" uniqKey="Goldenberg A" first="Alice" last="Goldenberg">Alice Goldenberg</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, CHU Charles Nicolle, Rouen</wicri:regionArea><placeName><region type="region">Région Normandie</region><region type="old region">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Van Heyningen, Veronica" sort="Van Heyningen, Veronica" uniqKey="Van Heyningen V" first="Veronica" last="Van Heyningen">Veronica Van Heyningen</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, INSERM U1163, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hôpital Necker‐Enfants Malades AP‐HP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Fitzpatrick, David" sort="Fitzpatrick, David" uniqKey="Fitzpatrick D" first="David" last="Fitzpatrick">David Fitzpatrick</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Kleinjan, Dirk A" sort="Kleinjan, Dirk A" uniqKey="Kleinjan D" first="Dirk A." last="Kleinjan">Dirk A. Kleinjan</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Visel, Axel" sort="Visel, Axel" uniqKey="Visel A" first="Axel" last="Visel">Axel Visel</name><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Genomics Division, Lawrence Berkeley National Laboratory, Berkeley</wicri:cityArea></affiliation><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>U.S. Department of Energy Joint Genome Institute, Walnut Creek</wicri:cityArea></affiliation><affiliation><wicri:noCountry code="subField">Merced</wicri:noCountry></affiliation></author><author><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes–Sorbonne Paris Cité, Institut Imagine, INSERM U1163, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hôpital Necker‐Enfants Malades AP‐HP, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Human Mutation</title><title level="j" type="alt">HUMAN MUTATION</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><biblScope unit="vol">35</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1011">1011</biblScope><biblScope unit="page" to="1020">1020</biblScope><biblScope unit="page-count">10</biblScope><date type="published" when="2014-08">2014-08</date></imprint><idno type="ISSN">1059-7794</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions, and duplications within a ∼2 Mb region upstream of SOX9 can recapitulate the CD–DSD phenotype fully or partially, suggesting the existence of an unusually large cis‐regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ∼1.2–1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harboring candidate craniofacial regulatory elements. In parallel, ChIP‐Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple noncoding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li><li>Suisse</li><li>États-Unis</li></country><region><li>Californie</li><li>Canton de Vaud</li><li>Haute-Normandie</li><li>Région Normandie</li><li>Victoria (État)</li><li>Écosse</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Lausanne</li><li>Melbourne</li><li>New York</li><li>Paris</li><li>Rouen</li><li>Édimbourg</li></settlement><orgName><li>Université Paris-Descartes</li><li>Université d'Édimbourg</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Gordon, Christopher T" sort="Gordon, Christopher T" uniqKey="Gordon C" first="Christopher T." last="Gordon">Christopher T. Gordon</name></region><name sortKey="Abadie, Veronique" sort="Abadie, Veronique" uniqKey="Abadie V" first="Véronique" last="Abadie">Véronique Abadie</name><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name><name sortKey="Benko, Sabina" sort="Benko, Sabina" uniqKey="Benko S" first="Sabina" last="Benko">Sabina Benko</name><name sortKey="Goldenberg, Alice" sort="Goldenberg, Alice" uniqKey="Goldenberg A" first="Alice" last="Goldenberg">Alice Goldenberg</name><name sortKey="Gordon, Christopher T" sort="Gordon, Christopher T" uniqKey="Gordon C" first="Christopher T." last="Gordon">Christopher T. Gordon</name><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name><name sortKey="Munnich, Arnold" sort="Munnich, Arnold" uniqKey="Munnich A" first="Arnold" last="Munnich">Arnold Munnich</name><name sortKey="Munnich, Arnold" sort="Munnich, Arnold" uniqKey="Munnich A" first="Arnold" last="Munnich">Arnold Munnich</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Attanasio, Catia" sort="Attanasio, Catia" uniqKey="Attanasio C" first="Catia" last="Attanasio">Catia Attanasio</name></region><name sortKey="Benko, Sabina" sort="Benko, Sabina" uniqKey="Benko S" first="Sabina" last="Benko">Sabina Benko</name><name sortKey="Pennacchio, Len A" sort="Pennacchio, Len A" uniqKey="Pennacchio L" first="Len A." last="Pennacchio">Len A. 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Kleinjan</name><name sortKey="Temple, I Karen" sort="Temple, I Karen" uniqKey="Temple I" first="I. Karen" last="Temple">I. Karen Temple</name><name sortKey="Van Heyningen, Veronica" sort="Van Heyningen, Veronica" uniqKey="Van Heyningen V" first="Veronica" last="Van Heyningen">Veronica Van Heyningen</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Tan, Tiong Y" sort="Tan, Tiong Y" uniqKey="Tan T" first="Tiong Y." last="Tan">Tiong Y. Tan</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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