A distal intergenic region controls pancreatic endocrine differentiation by acting as a transcriptional enhancer and as a polycomb response element
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Lineage-selective expression of developmental genes is dependent on the interplay between activating and repressive mechanisms. Gene activation is dependent on cell-specific transcription factors that recognize transcriptional enhancer sequences. Gene repression often depends on the recruitment of Polycomb group (PcG) proteins, although the sequences that underlie the recruitment of PcG proteins, also known as Polycomb response elements (PREs), remain poorly understood in vertebrates. While distal PREs have been identified in mammals, a role for positive-acting enhancers in PcG-mediated repression has not been described. Here we have used a highly efficient procedure based on lentiviral-mediated transgenesis to carry out in vivo fine-mapping of, cis-regulatory sequences that control lineage-specific activation of Neurog3, a master regulator of pancreatic endocrine differentiation. Our findings reveal an enhancer region that is sufficient to drive correct spacio-temporal expression of Neurog3 and demonstrate that this same region serves as a PRE in alternative lineages where Neurog3 is inactive.
Date Issued
2017-02-22
Date Acceptance
2017-01-02
Citation
PLOS ONE, 2017, 12 (2)
ISSN
1932-6203
Publisher
PUBLIC LIBRARY OF SCIENCE
Journal / Book Title
PLOS ONE
Volume
12
Issue
2
Copyright Statement
© 2017 van Arensbergen et al. This is
an open access article distributed under the terms
of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/),
which permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
an open access article distributed under the terms
of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/),
which permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Sponsor
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000394680900015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/L02036X/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GENE-EXPRESSION
PROGENITOR CELLS
BETA-CELLS
GROUP PROTEINS
HISTONE H2A
NEUROGENIN3
CHROMATIN
MICE
UBIQUITINATION
RECRUITMENT
General Science & Technology
MD Multidisciplinary
Publication Status
Published
Article Number
ARTN e0171508