Human pancreatic islet 3D chromatin architecture provides insights into the genetics of type 2 diabetes
By
Irene Miguel-Escalada,
Silvia Bonàs-Guarch,
Inês Cebola,
Ponsa-Cobas Joan,
Julen Mendieta-Esteban,
Delphine M.Y. Rolando,
Biola M. Javierre,
Goutham Atla,
Irene Farabella,
Claire C Morgan,
Javier García-Hurtado,
Anthony Beucher,
Ignasi Morán,
Lorenzo Pasquali,
Mireia Ramos,
Emil V.R. Appel,
Allan Linneberg,
Anette P. Gjesing,
Daniel R Witte,
Oluf Pedersen,
Niels Grarup,
Philippe Ravassard,
David Torrents,
Josep Maria Mercader,
Lorenzo Piemonti,
Thierry Berney,
Eelco J.P. Koning de,
Julie Kerr-Conte,
François Pattou,
Iryna O. Fedko,
Inga Prokopenko,
Torben Hansen,
Marc A. Marti-Renom,
Peter Fraser,
Jorge Ferrer
Posted 27 Aug 2018
bioRxiv DOI: 10.1101/400291
(published DOI: 10.1038/s41588-019-0457-0)
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 regions (enhancer clusters, stretch enhancers or super-enhancers). So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in 3D-space. Furthermore, their target genes are generally unknown. We have now created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers with their target genes, often located hundreds of kilobases away. It further revealed sets of islet enhancers, super-enhancers and active promoters that form 3D higher-order hubs, some of which show coordinated glucose-dependent activity. Hub genetic variants impact the heritability of insulin secretion, and help identify individuals in whom genetic variation of islet function is important for T2D. Human islet 3D chromatin architecture thus provides a framework for interpretation of T2D GWAS signals.
Download data
- Downloaded 2,493 times
- Download rankings, all-time:
- Site-wide: 4,647
- In genomics: 564
- Year to date:
- Site-wide: 39,158
- Since beginning of last month:
- Site-wide: 49,104
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!