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. © 2017 The Authors
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks / Akerman, I.; Tu, Z.; Beucher, A.; Rolando, D. M. Y.; Sauty Colace, C.; Benazra, M.; Nakic, N.; Yang, J.; Wang, H.; Pasquali, L.; Moran, I.; Garcia Hurtado, J.; Castro, N.; Gonzalez Franco, R.; Stewart, A. F.; Bonner, C.; Piemonti, Lorenzo; Berney, T.; Groop, L.; Kerr Conte, J.; Pattou, F.; Argmann, C.; Schadt, E.; Ravassard, P.; Ferrer, J.. - In: CELL METABOLISM. - ISSN 1550-4131. - 25:2(2017), pp. 400-411. [10.1016/j.cmet.2016.11.016]
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
PIEMONTI, LORENZO;
2017-01-01
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. © 2017 The AuthorsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
