Title :

Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes.

Author(s) :

Miguel-Escalada, Irene [Auteur]
Bonàs-Guarch, Silvia [Auteur]
Cebola, Inês [Auteur]
Ponsa-Cobas, Joan [Auteur]
Mendieta-Esteban, Julen [Auteur]
Atla, Goutham [Auteur]
Javierre, Biola M. [Auteur]
Rolando, Delphine M. Y. [Auteur]
Farabella, Irene [Auteur]
Morgan, Claire C. [Auteur]
García-Hurtado, Javier [Auteur]
Beucher, Anthony [Auteur]
Morán, Ignasi [Auteur]
Pasquali, Lorenzo [Auteur]
Ramos-Rodríguez, Mireia [Auteur]
Appel, Emil V. R. [Auteur]
Linneberg, Allan [Auteur]
Gjesing, Anette P. [Auteur]
Witte, Daniel R. [Auteur]
Pedersen, Oluf [Auteur]
Grarup, Niels [Auteur]
Ravassard, Philippe [Auteur]
Sorbonne Université [SU]
Centre National de la Recherche Scientifique [CNRS]
Université Pierre et Marie Curie - Paris 6 [UPMC]
Torrents, David [Auteur]
Mercader, Josep M. [Auteur]
Piemonti, Lorenzo [Auteur]
Berney, Thierry [Auteur]
De Koning, Eelco J. P. [Auteur]
Pattou Kerr-Conte, Julie [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Pattou, Francois [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Fedko, Iryna O. [Auteur]
Groop, Leif [Auteur]
Prokopenko, Inga [Auteur]
Hansen, Torben [Auteur]
Marti-Renom, Marc A. [Auteur]
Fraser, Peter [Auteur]
Ferrer, Jorge [Auteur]

Journal title :

Nature Genetics

Abbreviated title :

Nat. Genet.

Volume number :

51

Pages :

1137-1148

Publication date :

2019-07

ISSN :

1546-1718

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, ...
Show more >Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown. We have created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers to their target genes, often located hundreds of kilobases away. It also revealed >1,300 groups of islet enhancers, super-enhancers and active promoters that form 3D hubs, some of which show coordinated glucose-dependent activity. We demonstrate that genetic variation in hubs impacts insulin secretion heritability, and show that hub annotations can be used for polygenic scores that predict T2D risk driven by islet regulatory variants. Human islet 3D chromatin architecture, therefore, provides a framework for interpretation of T2D genome-wide association study (GWAS) signals.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Recherche translationnelle sur le diabète (RTD) - U1190

Submission date :

2024-01-19T23:50:41Z
2024-09-25T12:10:50Z