RT Journal Article
SR Electronic
T1 Human pancreatic β cell lncRNAs control cell-specific regulatory networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 096230
DO 10.1101/096230
A1 Ildem Akerman
A1 Zhidong Tu
A1 Anthony Beucher
A1 Delphine M.Y. Rolando
A1 Claire Sauty-Colace
A1 Marion Benazra
A1 Nikolina Nakic
A1 Jialiang Yang
A1 Huan Wang
A1 Lorenzo Pasquali
A1 Ignasi Moran
A1 Javier Garcia-Hurtado
A1 Natalia Castro
A1 Roser Gonzalez-Franco
A1 Andrew Stewart
A1 Caroline Bonner
A1 Lorenzo Piemonti
A1 Thierry Berney
A1 Leif Groop
A1 Julie Kerr-Conte
A1 Francois Pattou
A1 Carmen Argmann
A1 Eric Schadt
A1 Philippe Ravassard
A1 Jorge Ferrer
YR 2016
UL http://biorxiv.org/content/early/2016/12/23/096230.abstract
AB Recent studies have uncovered thousands of long non-coding RNAs (IncRNAs) 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 lncRNA PLUTO affects local three-dimensional 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.