Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants
- Autores
- Pasquali, Lorenzo; Gaulton, Kyle J.; Rodríguez Seguí, Santiago Andrés; Mularoni, Loris; Miguel Escalada, Irene; Akerman, Ildem; Tena, Juan J.; Morán, Ignasi; Gómez Marín, Carlos; Van De Bunt, Martijn; Ponsa Cobas, Joan; Castro, Natalia; Nammo, Takao; Cebola, Inês; García Hurtado, Javier; Maestro, Miguel Angel; Pattou, François; Piemonti, Lorenzo; Berney, Thierry; Gloyn, Anna L.; Ravassard, Philippe; Skarmeta, José Luis Gómez; Müller, Ferenc; Mccarthy, Mark I.; Ferrer, Jorge
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify trait-associated variants that disrupt DNA binding and islet enhancer activity. Our studies illustrate how islet transcription factors interact functionally with the epigenome and provide systematic evidence that the dysregulation of islet enhancers is relevant to the mechanisms underlying type 2 diabetes. © 2014 Nature America, Inc.
Fil: Pasquali, Lorenzo. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España
Fil: Gaulton, Kyle J.. Wellcome Trust Centre For Human Genetics; Reino Unido. Churchill Hospital; Reino Unido
Fil: Rodríguez Seguí, Santiago Andrés. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Mularoni, Loris. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España
Fil: Miguel Escalada, Irene. University Of Birmingham; Reino Unido
Fil: Akerman, Ildem. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España
Fil: Tena, Juan J.. Universidad Pablo de Olavide; España
Fil: Morán, Ignasi. Imperial College London; Reino Unido
Fil: Gómez Marín, Carlos. Universidad Pablo de Olavide; España
Fil: Van De Bunt, Martijn. Churchill Hospital; Reino Unido. Wellcome Trust Centre For Human Genetics; Reino Unido
Fil: Ponsa Cobas, Joan. Imperial College London; Reino Unido
Fil: Castro, Natalia. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España
Fil: Nammo, Takao. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. National Center For Global Health And Medicine; Japón
Fil: Cebola, Inês. Imperial College London; Reino Unido
Fil: García Hurtado, Javier. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Maestro, Miguel Angel. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España
Fil: Pattou, François. Universite Lille 2 ; Francia
Fil: Piemonti, Lorenzo. San Raffaele Scientific Institute; Italia
Fil: Berney, Thierry. Geneva University Hospitals and University of Geneva; Suiza
Fil: Gloyn, Anna L.. Churchill Hospital; Reino Unido
Fil: Ravassard, Philippe. Universite Pierre et Marie Curie; Francia
Fil: Skarmeta, José Luis Gómez. Universidad Pablo de Olavide; España
Fil: Müller, Ferenc. University Of Birmingham; Reino Unido
Fil: Mccarthy, Mark I.. Churchill Hospital; Reino Unido. Wellcome Trust Centre For Human Genetics; Reino Unido
Fil: Ferrer, Jorge. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Imperial College London; Reino Unido. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España - Materia
-
Beta Cell
Enhancer
Epigenomic
Type 2 Diabetes - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/36666
Ver los metadatos del registro completo
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Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variantsPasquali, LorenzoGaulton, Kyle J.Rodríguez Seguí, Santiago AndrésMularoni, LorisMiguel Escalada, IreneAkerman, IldemTena, Juan J.Morán, IgnasiGómez Marín, CarlosVan De Bunt, MartijnPonsa Cobas, JoanCastro, NataliaNammo, TakaoCebola, InêsGarcía Hurtado, JavierMaestro, Miguel AngelPattou, FrançoisPiemonti, LorenzoBerney, ThierryGloyn, Anna L.Ravassard, PhilippeSkarmeta, José Luis GómezMüller, FerencMccarthy, Mark I.Ferrer, JorgeBeta CellEnhancerEpigenomicType 2 Diabeteshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify trait-associated variants that disrupt DNA binding and islet enhancer activity. Our studies illustrate how islet transcription factors interact functionally with the epigenome and provide systematic evidence that the dysregulation of islet enhancers is relevant to the mechanisms underlying type 2 diabetes. © 2014 Nature America, Inc.Fil: Pasquali, Lorenzo. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); EspañaFil: Gaulton, Kyle J.. Wellcome Trust Centre For Human Genetics; Reino Unido. Churchill Hospital; Reino UnidoFil: Rodríguez Seguí, Santiago Andrés. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Mularoni, Loris. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; EspañaFil: Miguel Escalada, Irene. University Of Birmingham; Reino UnidoFil: Akerman, Ildem. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); EspañaFil: Tena, Juan J.. Universidad Pablo de Olavide; EspañaFil: Morán, Ignasi. Imperial College London; Reino UnidoFil: Gómez Marín, Carlos. Universidad Pablo de Olavide; EspañaFil: Van De Bunt, Martijn. Churchill Hospital; Reino Unido. Wellcome Trust Centre For Human Genetics; Reino UnidoFil: Ponsa Cobas, Joan. Imperial College London; Reino UnidoFil: Castro, Natalia. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; EspañaFil: Nammo, Takao. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. National Center For Global Health And Medicine; JapónFil: Cebola, Inês. Imperial College London; Reino UnidoFil: García Hurtado, Javier. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; EspañaFil: Maestro, Miguel Angel. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; EspañaFil: Pattou, François. Universite Lille 2 ; FranciaFil: Piemonti, Lorenzo. San Raffaele Scientific Institute; ItaliaFil: Berney, Thierry. Geneva University Hospitals and University of Geneva; SuizaFil: Gloyn, Anna L.. Churchill Hospital; Reino UnidoFil: Ravassard, Philippe. Universite Pierre et Marie Curie; FranciaFil: Skarmeta, José Luis Gómez. Universidad Pablo de Olavide; EspañaFil: Müller, Ferenc. University Of Birmingham; Reino UnidoFil: Mccarthy, Mark I.. Churchill Hospital; Reino Unido. Wellcome Trust Centre For Human Genetics; Reino UnidoFil: Ferrer, Jorge. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Imperial College London; Reino Unido. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; EspañaNature Publishing Group2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36666Pasquali, Lorenzo; Gaulton, Kyle J.; Rodríguez Seguí, Santiago Andrés; Mularoni, Loris; Miguel Escalada, Irene; et al.; Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants; Nature Publishing Group; Nature Genetics; 46; 2; 1-2014; 136-1431061-4036CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/ng.2870info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:33:35Zoai:ri.conicet.gov.ar:11336/36666instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:33:36.271CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| title |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| spellingShingle |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants Pasquali, Lorenzo Beta Cell Enhancer Epigenomic Type 2 Diabetes |
| title_short |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| title_full |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| title_fullStr |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| title_full_unstemmed |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| title_sort |
Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants |
| dc.creator.none.fl_str_mv |
Pasquali, Lorenzo Gaulton, Kyle J. Rodríguez Seguí, Santiago Andrés Mularoni, Loris Miguel Escalada, Irene Akerman, Ildem Tena, Juan J. Morán, Ignasi Gómez Marín, Carlos Van De Bunt, Martijn Ponsa Cobas, Joan Castro, Natalia Nammo, Takao Cebola, Inês García Hurtado, Javier Maestro, Miguel Angel Pattou, François Piemonti, Lorenzo Berney, Thierry Gloyn, Anna L. Ravassard, Philippe Skarmeta, José Luis Gómez Müller, Ferenc Mccarthy, Mark I. Ferrer, Jorge |
| author |
Pasquali, Lorenzo |
| author_facet |
Pasquali, Lorenzo Gaulton, Kyle J. Rodríguez Seguí, Santiago Andrés Mularoni, Loris Miguel Escalada, Irene Akerman, Ildem Tena, Juan J. Morán, Ignasi Gómez Marín, Carlos Van De Bunt, Martijn Ponsa Cobas, Joan Castro, Natalia Nammo, Takao Cebola, Inês García Hurtado, Javier Maestro, Miguel Angel Pattou, François Piemonti, Lorenzo Berney, Thierry Gloyn, Anna L. Ravassard, Philippe Skarmeta, José Luis Gómez Müller, Ferenc Mccarthy, Mark I. Ferrer, Jorge |
| author_role |
author |
| author2 |
Gaulton, Kyle J. Rodríguez Seguí, Santiago Andrés Mularoni, Loris Miguel Escalada, Irene Akerman, Ildem Tena, Juan J. Morán, Ignasi Gómez Marín, Carlos Van De Bunt, Martijn Ponsa Cobas, Joan Castro, Natalia Nammo, Takao Cebola, Inês García Hurtado, Javier Maestro, Miguel Angel Pattou, François Piemonti, Lorenzo Berney, Thierry Gloyn, Anna L. Ravassard, Philippe Skarmeta, José Luis Gómez Müller, Ferenc Mccarthy, Mark I. Ferrer, Jorge |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Beta Cell Enhancer Epigenomic Type 2 Diabetes |
| topic |
Beta Cell Enhancer Epigenomic Type 2 Diabetes |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify trait-associated variants that disrupt DNA binding and islet enhancer activity. Our studies illustrate how islet transcription factors interact functionally with the epigenome and provide systematic evidence that the dysregulation of islet enhancers is relevant to the mechanisms underlying type 2 diabetes. © 2014 Nature America, Inc. Fil: Pasquali, Lorenzo. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España Fil: Gaulton, Kyle J.. Wellcome Trust Centre For Human Genetics; Reino Unido. Churchill Hospital; Reino Unido Fil: Rodríguez Seguí, Santiago Andrés. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Mularoni, Loris. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España Fil: Miguel Escalada, Irene. University Of Birmingham; Reino Unido Fil: Akerman, Ildem. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); España Fil: Tena, Juan J.. Universidad Pablo de Olavide; España Fil: Morán, Ignasi. Imperial College London; Reino Unido Fil: Gómez Marín, Carlos. Universidad Pablo de Olavide; España Fil: Van De Bunt, Martijn. Churchill Hospital; Reino Unido. Wellcome Trust Centre For Human Genetics; Reino Unido Fil: Ponsa Cobas, Joan. Imperial College London; Reino Unido Fil: Castro, Natalia. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España Fil: Nammo, Takao. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. National Center For Global Health And Medicine; Japón Fil: Cebola, Inês. Imperial College London; Reino Unido Fil: García Hurtado, Javier. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España Fil: Maestro, Miguel Angel. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España Fil: Pattou, François. Universite Lille 2 ; Francia Fil: Piemonti, Lorenzo. San Raffaele Scientific Institute; Italia Fil: Berney, Thierry. Geneva University Hospitals and University of Geneva; Suiza Fil: Gloyn, Anna L.. Churchill Hospital; Reino Unido Fil: Ravassard, Philippe. Universite Pierre et Marie Curie; Francia Fil: Skarmeta, José Luis Gómez. Universidad Pablo de Olavide; España Fil: Müller, Ferenc. University Of Birmingham; Reino Unido Fil: Mccarthy, Mark I.. Churchill Hospital; Reino Unido. Wellcome Trust Centre For Human Genetics; Reino Unido Fil: Ferrer, Jorge. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Imperial College London; Reino Unido. Institut d’Investigacions Biomèdiques August Pi i Sunyer ; España |
| description |
Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify trait-associated variants that disrupt DNA binding and islet enhancer activity. Our studies illustrate how islet transcription factors interact functionally with the epigenome and provide systematic evidence that the dysregulation of islet enhancers is relevant to the mechanisms underlying type 2 diabetes. © 2014 Nature America, Inc. |
| publishDate |
2014 |
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2014-01 |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/36666 Pasquali, Lorenzo; Gaulton, Kyle J.; Rodríguez Seguí, Santiago Andrés; Mularoni, Loris; Miguel Escalada, Irene; et al.; Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants; Nature Publishing Group; Nature Genetics; 46; 2; 1-2014; 136-143 1061-4036 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/36666 |
| identifier_str_mv |
Pasquali, Lorenzo; Gaulton, Kyle J.; Rodríguez Seguí, Santiago Andrés; Mularoni, Loris; Miguel Escalada, Irene; et al.; Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants; Nature Publishing Group; Nature Genetics; 46; 2; 1-2014; 136-143 1061-4036 CONICET Digital CONICET |
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eng |
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eng |
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Nature Publishing Group |
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Nature Publishing Group |
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