UNIGE document Scientific Article
previous document  unige:89724  next document
add to browser collection
Title

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

Authors
Schmidt, Søren Fisker
Madsen, Jesper Grud Skat
Frafjord, Kari Østerli
Poulsen, Lars la Cour
Salö, Sofia
Boergesen, Michael
Loft, Anne
Larsen, Bjørk Ditlev
show hidden authors show all authors [1 - 13]
Published in Cell Reports. 2016, vol. 16, no. 9, p. 2359-2372
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.
Identifiers
PMID: 27545881
Full text
Article (Published version) (4.5 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Mitochondries et sécrétion d'insuline (671)
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. https://archive-ouverte.unige.ch/unige:89724

65 hits

1 download

Update

Deposited on : 2016-12-02

Export document
Format :
Citation style :