Long non-coding RNAs as local regulators of pancreatic islet transcription factor genes
Author(s)
Font-Cunill, Berta
Arnes, Luis
Ferrer, Jorge
Sussel, Lori
Beucher, Anthony
Type
Journal Article
Abstract
The transcriptional programs of differentiated cells are tightly regulated by interactions between cell type-specific transcription factors and cis-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 cis or trans, 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 cis-regulation. In this review, we discuss current knowledge of molecular mechanisms underlying cis-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 cis-regulation of TF genes. We propose that cis-regulatory lncRNAs could represent a molecular target for modulation of diabetes-relevant genes.
Date Issued
2018-11-06
Date Acceptance
2018-10-18
Citation
Frontiers in Genetics, 2018, 9, pp.1-9
ISSN
1664-8021
Publisher
Frontiers Media
Start Page
1
End Page
9
Journal / Book Title
Frontiers in Genetics
Volume
9
Copyright Statement
© 2018 Font-Cunill, Arnes, Ferrer, Sussel and Beucher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000449248900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/L02036X/1
MR/L02036X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
long non-coding RNAs
transcription factors
pancreatic islets
beta cells
cis-regulation
BETA-CELL TRANSCRIPTOME
ANTISENSE TRANSCRIPTION
LINEAGE COMMITMENT
EXPRESSION
ACTIVATION
CHROMATIN
LNCRNA
CRISPR
DIFFERENTIATION
LOCUS
Publication Status
Published
Article Number
ARTN 524
Date Publish Online
2018-11-06