![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
5MB | |
![[img]](http://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplemental Information)
159MB |
| Item Type: | Article |
|---|---|
| Title: | Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines |
| Creators Name: | Benaglio, P. and Zhu, H. and Okino, M.L. and Yan, J. and Elgamal, R. and Nariai, N. and Beebe, E. and Korgaonkar, K. and Qiu, Y. and Donovan, M.K.R. and Chiou, J. and Wang, G. and Newsome, J. and Kaur, J. and Miller, M. and Preissl, S. and Corban, S. and Aylward, A. and Taipale, J. and Ren, B. and Frazer, K.A. and Sander, M. and Gaulton, K.J. |
| Abstract: | We combined functional genomics and human genetics to investigate processes that affect type 1 diabetes (T1D) risk by mediating beta cell survival in response to proinflammatory cytokines. We mapped 38,931 cyto- kine-responsive candidate cis-regulatory elements (cCREs) in beta cells using ATAC-seq and snATAC-seq and linked them to target genes using co-accessibility and HiChIP. Using a genome-wide CRISPR screen in EndoC-bH1 cells, we identified 867 genes affecting cytokine-induced survival, and genes promoting survival and up-regulated in cytokines were enriched at T1D risk loci. Using SNP-SELEX, we identified 2,229 variants in cytokine-responsive cCREs altering transcription factor (TF) binding, and variants altering binding of TFs regulating stress, inflammation, and apoptosis were enriched for T1D risk. At the 16p13 locus, a fine-mapped T1D variant altering TF binding in a cytokine-induced cCRE interacted with SOCS1, which pro- moted survival in cytokine exposure. Our findings reveal processes and genes acting in beta cells during inflammation that modulate T1D risk. |
| Keywords: | Type 1 Diabetes, Beta Cell, Proinflammatory Cytokines, Functional Genomics, Accessible Chromatin, 3D Chromatin Interactions, Gene Expression, Human Genetics, CRISPR Screen, High-Throughput Reporter Assay |
| Source: | Cell Genomics |
| ISSN: | 2666-979X |
| Publisher: | Cell Press |
| Volume: | 2 |
| Number: | 12 |
| Page Range: | 100214 |
| Date: | 14 December 2022 |
| Official Publication: | https://doi.org/10.1016/j.xgen.2022.100214 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
