Human pancreatic β cell lncRNAs control cell-specific regulatory networks

Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M. Y. Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F. Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-ConteFrancois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)400-411
Number of pages12
JournalCell Metabolism
Volume25
Issue number2
Early online date29 Dec 2016
DOIs
Publication statusPublished - 7 Feb 2017

Keywords

  • Chromatin
  • Diabetes Mellitus, Type 2
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Gene Regulatory Networks
  • Homeodomain Proteins
  • Humans
  • Insulin
  • Insulin-Secreting Cells
  • Multigene Family
  • Phenotype
  • RNA, Long Noncoding
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Journal Article

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