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

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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

Schmidt, SF, Madsen, JGS, Frafjord, KØ, Poulsen, LLC, Salö, S, Boergesen, M, Loft, A, Larsen, BD, Madsen, MS, Holst, JJ, Maechler, P, Dalgaard, LT & Mandrup, S 2016, 'Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells', Cell Reports, vol. 16, no. 9, pp. 2359-72. https://doi.org/10.1016/j.celrep.2016.07.063

APA

Schmidt, S. F., Madsen, J. G. S., Frafjord, K. Ø., Poulsen, L. L. C., Salö, S., Boergesen, M., Loft, A., Larsen, B. D., Madsen, M. S., Holst, J. J., Maechler, P., Dalgaard, L. T., & Mandrup, S. (2016). Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells. Cell Reports, 16(9), 2359-72. https://doi.org/10.1016/j.celrep.2016.07.063

Vancouver

Schmidt SF, Madsen JGS, Frafjord KØ, Poulsen LLC, Salö S, Boergesen M et al. Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells. Cell Reports. 2016 Aug 30;16(9):2359-72. https://doi.org/10.1016/j.celrep.2016.07.063

Author

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. / Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells. In: Cell Reports. 2016 ; Vol. 16, No. 9. pp. 2359-72.

Bibtex

@article{6af2a742d4544240b465e5a750113604,
title = "Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells",
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.",
keywords = "Journal Article",
author = "Schmidt, {S{\o}ren Fisker} and Madsen, {Jesper Grud Skat} and Frafjord, {Kari {\O}sterli} and Poulsen, {Lars la Cour} and Sofia Sal{\"o} and Michael Boergesen and Anne Loft and Larsen, {Bj{\o}rk Ditlev} and Madsen, {Maria Stahl} and Holst, {Jens Juul} and Pierre Maechler and Dalgaard, {Louise Torp} and Susanne Mandrup",
note = "Copyright {\textcopyright} 2016 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = aug,
day = "30",
doi = "10.1016/j.celrep.2016.07.063",
language = "English",
volume = "16",
pages = "2359--72",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",

}

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