en
Scientific article
Open access
English

Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells

Published inCell reports, vol. 16, no. 9, p. 2359-2372
Publication date2016
Abstract

Glucose is an important inducer of insulin secretion, but it also stimulates long-term adaptive changes in gene expression that can either promote or antagonize the proliferative potential and function of β cells. Here, we have generated time-resolved profiles of enhancer and transcriptional activity in response to glucose in the INS-1E pancreatic β cell line. Our data outline a biphasic response with a first transcriptional wave during which metabolic genes are activated, and a second wave where cell-cycle genes are activated and β cell identity genes are repressed. The glucose-sensing transcription factor ChREBP directly activates first wave enhancers, whereas repression and activation of second wave enhancers are indirect. By integrating motif enrichment within late-regulated enhancers with expression profiles of the associated transcription factors, we have identified multiple putative regulators of the second wave. These include RORγ, the activity of which is important for glucose-induced proliferation of both INS-1E and primary rat β cells.

Citation (ISO format)
SCHMIDT, Søren Fisker et al. Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells. In: Cell reports, 2016, vol. 16, n° 9, p. 2359–2372. doi: 10.1016/j.celrep.2016.07.063
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal2211-1247
460views
112downloads

Technical informations

Creation10/04/2016 11:35:00 AM
First validation10/04/2016 11:35:00 AM
Update time03/15/2023 1:03:14 AM
Status update03/15/2023 1:03:13 AM
Last indexation05/02/2024 5:59:14 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack