Long Non-coding RNAs as Local Regulators of Pancreatic Islet Transcription Factor Genes.

The transcriptional programs of differentiated cells are tightly regulated by interactions between cell type-specific transcription factors and -regulatory elements. Long non-coding RNAs (lncRNAs) have emerged as additional regulators of gene transcription. Current evidence indicates that lncRNAs are a very heterogeneous group of molecules. For example, selected lncRNAs have been shown to regulate gene expression in or , although in most cases the precise underlying molecular mechanisms is unknown. Recent studies have uncovered a large number of lncRNAs that are selectively expressed in pancreatic islet cells, some of which were shown to regulate β cell transcriptional programs. A subset of such islet lncRNAs appears to control the expression of β cell-specific transcription factor (TF) genes by local -regulation. In this review, we discuss current knowledge of molecular mechanisms underlying -regulatory lncRNAs and discuss challenges involved in using genetic perturbations to define their function. We then discuss known examples of pancreatic islet lncRNAs that appear to exert -regulation of TF genes. We propose that -regulatory lncRNAs could represent a molecular target for modulation of diabetes-relevant genes.