AUTHOR=Font-Cunill Berta , Arnes Luis , Ferrer Jorge , Sussel Lori , Beucher Anthony 

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

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00524

DOI=10.3389/fgene.2018.00524

ISSN=1664-8021

ABSTRACT=<p>The transcriptional programs of differentiated cells are tightly regulated by interactions between cell type-specific transcription factors and <italic>cis</italic>-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 <italic>cis</italic> or <italic>trans</italic>, 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 <italic>cis</italic>-regulation. In this review, we discuss current knowledge of molecular mechanisms underlying <italic>cis</italic>-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 <italic>cis</italic>-regulation of TF genes. We propose that <italic>cis</italic>-regulatory lncRNAs could represent a molecular target for modulation of diabetes-relevant genes.</p>