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Quagliarini, F. ; Mir, A.A. ; Balazs, K. ; Wierer, M.* ; Dyar, K.A. ; Jouffe, C. ; Makris, K. ; Hawe, J. ; Heinig, M. ; Filipp, F.V. ; Barish, G.D.* ; Uhlenhaut, N.H.

Cistromic reprogramming of the diurnal glucocorticoid hormone response by high-fat diet.

Mol. Cell 76, 531-545.e5 (2019)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Circadian Clock ; Cistromes ; Glucocorticoid Receptor ; Glucose And Lipid Metabolism ; High-fat Diet ; Hormones ; Mouse Liver ; Pparα ; Stat5; Rev-erb-alpha; Hepatic Growth-hormone; Circadian Clock; Peripheral-tissues; Transcriptional Architecture; Hepatocellular-carcinoma; Nuclear Receptors; Read Alignment; Ppar-alpha; Metabolism
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Zeitschrift Molecular Cell
Quellenangaben Band: 76, Heft: 4, Seiten: 531-545.e5 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Obesity (IDO)
Institute of Computational Biology (ICB)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-501900-227
G-502200-001
G-503891-001
G-502594-001
G-553500-001
G-503800-001
DOI 10.1016/j.molcel.2019.10.007
WOS ID WOS:000497994500002
Scopus ID 85074967809
PubMed ID 31706703
Erfassungsdatum 2019-11-11
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