REVERBa couples the circadian clock to hepatic glucocorticoid actionCitation formats

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REVERBa couples the circadian clock to hepatic glucocorticoid action. / Caratti, Giorgio; Iqbal, Mudassar; Hunter, Louise; Kim, Donghwan; Wang, Ping; Vonslow, Ryan M; Begley, Nicola; Tetley, Abigail J; Woodburn, Joanna L; Pariollaud, Marie; Maidstone, Robert; Donaldson, Ian J; Zhang, Zhenguang; Ince, Louise M; Kitchen, Gareth; Baxter, Matthew; Poolman, Toryn M; Daniels, Dion A; Stirling, David R; Brocker, Chad; Gonzalez, Frank; Loudon, Andrew Si; Bechtold, David A; Rattray, Magnus; Matthews, Laura C; Ray, David W.

In: The Journal of clinical investigation, Vol. 128, No. 10, 01.10.2018, p. 4454-4471.

Research output: Contribution to journalArticle

Harvard

Caratti, G, Iqbal, M, Hunter, L, Kim, D, Wang, P, Vonslow, RM, Begley, N, Tetley, AJ, Woodburn, JL, Pariollaud, M, Maidstone, R, Donaldson, IJ, Zhang, Z, Ince, LM, Kitchen, G, Baxter, M, Poolman, TM, Daniels, DA, Stirling, DR, Brocker, C, Gonzalez, F, Loudon, AS, Bechtold, DA, Rattray, M, Matthews, LC & Ray, DW 2018, 'REVERBa couples the circadian clock to hepatic glucocorticoid action' The Journal of clinical investigation, vol. 128, no. 10, pp. 4454-4471. https://doi.org/10.1172/JCI96138

APA

Caratti, G., Iqbal, M., Hunter, L., Kim, D., Wang, P., Vonslow, R. M., ... Ray, D. W. (2018). REVERBa couples the circadian clock to hepatic glucocorticoid action. The Journal of clinical investigation, 128(10), 4454-4471. https://doi.org/10.1172/JCI96138

Vancouver

Caratti G, Iqbal M, Hunter L, Kim D, Wang P, Vonslow RM et al. REVERBa couples the circadian clock to hepatic glucocorticoid action. The Journal of clinical investigation. 2018 Oct 1;128(10):4454-4471. https://doi.org/10.1172/JCI96138

Author

Caratti, Giorgio ; Iqbal, Mudassar ; Hunter, Louise ; Kim, Donghwan ; Wang, Ping ; Vonslow, Ryan M ; Begley, Nicola ; Tetley, Abigail J ; Woodburn, Joanna L ; Pariollaud, Marie ; Maidstone, Robert ; Donaldson, Ian J ; Zhang, Zhenguang ; Ince, Louise M ; Kitchen, Gareth ; Baxter, Matthew ; Poolman, Toryn M ; Daniels, Dion A ; Stirling, David R ; Brocker, Chad ; Gonzalez, Frank ; Loudon, Andrew Si ; Bechtold, David A ; Rattray, Magnus ; Matthews, Laura C ; Ray, David W. / REVERBa couples the circadian clock to hepatic glucocorticoid action. In: The Journal of clinical investigation. 2018 ; Vol. 128, No. 10. pp. 4454-4471.

Bibtex

@article{3b7e615953dd455dbadfa79c9d079f6e,
title = "REVERBa couples the circadian clock to hepatic glucocorticoid action",
abstract = "The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism.",
author = "Giorgio Caratti and Mudassar Iqbal and Louise Hunter and Donghwan Kim and Ping Wang and Vonslow, {Ryan M} and Nicola Begley and Tetley, {Abigail J} and Woodburn, {Joanna L} and Marie Pariollaud and Robert Maidstone and Donaldson, {Ian J} and Zhenguang Zhang and Ince, {Louise M} and Gareth Kitchen and Matthew Baxter and Poolman, {Toryn M} and Daniels, {Dion A} and Stirling, {David R} and Chad Brocker and Frank Gonzalez and Loudon, {Andrew Si} and Bechtold, {David A} and Magnus Rattray and Matthews, {Laura C} and Ray, {David W}",
year = "2018",
month = "10",
day = "1",
doi = "10.1172/JCI96138",
language = "English",
volume = "128",
pages = "4454--4471",
journal = "The Journal of clinical investigation",
issn = "1558-8238",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

RIS

TY - JOUR

T1 - REVERBa couples the circadian clock to hepatic glucocorticoid action

AU - Caratti, Giorgio

AU - Iqbal, Mudassar

AU - Hunter, Louise

AU - Kim, Donghwan

AU - Wang, Ping

AU - Vonslow, Ryan M

AU - Begley, Nicola

AU - Tetley, Abigail J

AU - Woodburn, Joanna L

AU - Pariollaud, Marie

AU - Maidstone, Robert

AU - Donaldson, Ian J

AU - Zhang, Zhenguang

AU - Ince, Louise M

AU - Kitchen, Gareth

AU - Baxter, Matthew

AU - Poolman, Toryn M

AU - Daniels, Dion A

AU - Stirling, David R

AU - Brocker, Chad

AU - Gonzalez, Frank

AU - Loudon, Andrew Si

AU - Bechtold, David A

AU - Rattray, Magnus

AU - Matthews, Laura C

AU - Ray, David W

PY - 2018/10/1

Y1 - 2018/10/1

N2 - The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism.

AB - The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism.

U2 - 10.1172/JCI96138

DO - 10.1172/JCI96138

M3 - Article

VL - 128

SP - 4454

EP - 4471

JO - The Journal of clinical investigation

JF - The Journal of clinical investigation

SN - 1558-8238

IS - 10

ER -