دورية أكاديمية
Primate-specific ZNF808 is essential for pancreatic development in humans
| العنوان: | Primate-specific ZNF808 is essential for pancreatic development in humans |
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| المؤلفون: | De Franco, E, Owens, NDL, Montaser, H, Wakeling, MN, Saarimäki-Vire, J, Triantou, A, Ibrahim, H, Balboa, D, Caswell, RC, Jennings, RE, Kvist, JA, Johnson, MB, Muralidharan, S, Ellard, S, Wright, CF, Maddirevula, S, Alkuraya, FS, Hanley, NA, Flanagan, SE, Otonkoski, T, Hattersley, AT, Imbeault, M |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2023 |
| المجموعة: | University of Exeter: Open Research Exeter (ORE) |
| الوصف: | This is the final version. Available on open access from Nature Research via the DOI in this record ; Data availability: Clinical and genotype data are available only through collaboration as this can be used to identify individuals and so cannot be made openly available. Requests for collaboration will be considered following an application to the Genetic Beta Cell Research Bank (https://www.diabetesgenes.org/current-research/genetic-beta-cell-research-bankTest/). Contact by email should be directed to A. Hattersley (A.T.Hattersley@exeter.ac.uk). All requests for access to data will be responded to within 28 days. Transcriptomic and epigenomic data for WT and ZNF808 KO are available from the NCBI Gene Expression Omnibus under accession GSE205164. Source data are provided with this paper. ; Code availability: Code and software versions used to analyze the data presented are indicated in the Methods and provided in https://github.com/owensnick/ZNF808Genomics.jlTest with persistent Zenodo https://doi.org/10.5281/zenodo.8375708Test. ; Identifying genes linked to extreme phenotypes in humans has the potential to highlight new biological processes not shared with all other mammals. Here we report the identification of homozygous loss-of-function variants in the primate-specific gene ZNF808 as a cause of pancreatic agenesis. ZNF808 is a member of the KRAB zinc finger protein (KZFPs) family, a large and rapidly evolving group of epigenetic silencers that target transposable elements. We show that loss of ZNF808 in vitro results in aberrant activation of regulatory potential contained in the primate-specific transposable elements it represses during early pancreas development. This leads to inappropriate specification of cell fate with induction of genes associated with liver identity. Our results highlight the essential role of ZNF808 for pancreatic development in humans and the contribution of primate-specific regions of the human genome to disease. This is the first report of loss of a primate-specific gene causing a congenital ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1546-1718 |
| العلاقة: | https://www.diabetesgenes.org/current-research/genetic-beta-cell-research-bankTest/; https://github.com/owensnick/ZNF808Genomics.jlTest; https://doi.org/10.5281/zenodo.8375708Test; orcid:0000-0002-1437-7891 (De Franco, Elisa); Vol. 55, pp. 2075–2081; 224600/Z/21/Z; WT098395/Z/12/Z; 105636/Z/14/Z; 19/005971; 20/0006263; 206688/Z/17/Z; MR/000638/1; MR/S036121/1; 312437; 0057286; ALTF 295-2019; RG-2022-010; http://hdl.handle.net/10871/133654Test; Nature Genetics |
| DOI: | 10.1038/s41588-023-01565-x |
| الإتاحة: | https://doi.org/10.1038/s41588-023-01565-xTest https://doi.org/10.5281/zenodo.8375708Test http://hdl.handle.net/10871/133654Test |
| حقوق: | © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0Test/ ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.D99D9CD7 |
| قاعدة البيانات: | BASE |
| تدمد: | 15461718 |
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| DOI: | 10.1038/s41588-023-01565-x |