Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells. / Schmidt, Søren Fisker; Madsen, Jesper Grud Skat; Frafjord, Kari Østerli; Poulsen, Lars la Cour; Salö, Sofia; Boergesen, Michael; Loft, Anne; Larsen, Bjørk Ditlev; Madsen, Maria Stahl; Holst, Jens Juul; Maechler, Pierre; Dalgaard, Louise Torp; Mandrup, Susanne.
In: Cell Reports, Vol. 16, No. 9, 30.08.2016, p. 2359-72.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells
AU - Schmidt, Søren Fisker
AU - Madsen, Jesper Grud Skat
AU - Frafjord, Kari Østerli
AU - Poulsen, Lars la Cour
AU - Salö, Sofia
AU - Boergesen, Michael
AU - Loft, Anne
AU - Larsen, Bjørk Ditlev
AU - Madsen, Maria Stahl
AU - Holst, Jens Juul
AU - Maechler, Pierre
AU - Dalgaard, Louise Torp
AU - Mandrup, Susanne
N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2016/8/30
Y1 - 2016/8/30
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.celrep.2016.07.063
DO - 10.1016/j.celrep.2016.07.063
M3 - Journal article
C2 - 27545881
VL - 16
SP - 2359
EP - 2372
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
ER -
ID: 165935824