Human Pancreatic ? Cell lncRNAs Control Cell-Specific Regulatory Networks.

ABSTRACT: Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic ? cells. ? 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 ? cell gene regulation and diabetes, the function of ? cell lncRNAs remains largely unknown. In this study, we investigated the function of ? 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 ? cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key ? 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 ? cell-specific transcription factor networks.

SUBMITTER: Akerman I 

PROVIDER: S-EPMC5300904 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other