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 language | English |
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Pages (from-to) | 400-411 |
Number of pages | 12 |
Journal | Cell Metabolism |
Volume | 25 |
Issue number | 2 |
Early online date | 29 Dec 2016 |
DOIs | |
Publication status | Published - 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