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Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

Akerman, Ildem
Tu, Zhidong
Beucher, Anthony
Rolando, Delphine M Y
Sauty-Colace, Claire
Benazra, Marion
Nakic, Nikolina
Yang, Jialiang
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Published in Cell metabolism. 2017, vol. 25, no. 2, p. 400-411
Abstract Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
Keywords CRISPR interferencePDX1PLUTOchromatindiabeteslncRNAslong noncoding RNAspancreatic isletstranscriptional networkstype 2 diabetes
PMID: 28041957
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Research groups La transplantation d'îlots de Langerhans (623)
Transplantation et hépatologie (905)
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AKERMAN, Ildem et al. Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks. In: Cell metabolism, 2017, vol. 25, n° 2, p. 400-411. doi: 10.1016/j.cmet.2016.11.016 https://archive-ouverte.unige.ch/unige:93706

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Deposited on : 2017-04-21

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