Human pancreatic β cell lncRNAs control cell-specific regulatory networks

Akerman, I.; Tu, Z.; Beucher, A.; Rolando, D.; 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, L.; Berney, T.; Groop, L.; Kerr-Conte, J.; Pattou, F.; Argmann, C.; Schadt, E.; Ravassard, P.; Ferrer, J.

doi:10.1101/096230

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bioRxiv · 10.1101/096230

Human pancreatic β cell lncRNAs control cell-specific regulatory networks

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Abstract

Recent studies have uncovered thousands of long non-coding RNAs (IncRNAs) in human pancreatic {beta} cells. {beta} 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 {beta} cell gene regulation and diabetes, the function of {beta} cell lncRNAs remains largely unknown. In this study, we investigated the function of {beta} 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 {beta} cell-specific transcriptional networks. We further demonstrate that lncRNA PLUTO affects local three-dimensional chromatin structure and transcription of PDX1, encoding a key {beta} 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 {beta} cell-specific transcription factor networks.

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Akerman, I., Tu, Z., Beucher, A., Rolando, D., 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, L., Berney, T., Groop, L., Kerr-Conte, J., Pattou, F., Argmann, C., Schadt, E., Ravassard, P., Ferrer, J.. 2016-12-23. Human pancreatic β cell lncRNAs control cell-specific regulatory networks. https://doi.org/10.1101/096230

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