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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; Wang, Huan L. and Pasquali, Lorenzo, et al. (2017) In Cell Metabolism 25(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... (More)

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.

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@article{28c0f789-ce8e-46e1-805b-d7d4a577fcfa,
  abstract     = {<p>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.</p>},
  author       = {Akerman, Ildem and Tu, Zhidong and Beucher, Anthony and Rolando, Delphine M Y and Sauty-Colace, Claire and Benazra, Marion and Nakic, Nikolina and Yang, Jialiang and Wang, Huan L. and Pasquali, Lorenzo and Moran, Ignasi and Garcia-Hurtado, Javier and Castro, Natalia and Gonzalez-Franco, Roser and Stewart, Andrew F. and Bonner, Caroline and Piemonti, Lorenzo and Berney, Thierry and Groop, Leif and Kerr-Conte, Julie and Pattou, Francois and Argmann, Carmen and Schadt, Eric and Ravassard, Philippe and Ferrer, Jorge},
  issn         = {1550-4131},
  keyword      = {chromatin,CRISPR interference,diabetes,lncRNAs,long noncoding RNAs,pancreatic islets,PDX1,PLUTO,transcriptional networks,type 2 diabetes},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {400--411},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks},
  url          = {http://dx.doi.org/10.1016/j.cmet.2016.11.016},
  volume       = {25},
  year         = {2017},
}