Zirkadiane Uhr; Tageslängenveränderung; Chronotherapie; Lebermetabolismus
Mang Géraldine M, La Spada Francesco, Emmenegger Yann, Chappuis Sylvie, Ripperger Jürgen A, Albrecht Urs, Franken Paul (2016), Altered Sleep Homeostasis in Rev-erbα Knockout Mice., in Sleep
, 39(3), 589-601.
Chavan Rohit, Feillet Céline, Costa Sara S Fonseca, Delorme James E, Okabe Takashi, Ripperger Jürgen A, Albrecht Urs (2016), Liver-derived ketone bodies are necessary for food anticipation., in Nature communications
, 7, 10580-10580.
Okabe Takashi, Chavan Rohit, Fonseca Costa Sara S, Brenna Andrea, Ripperger Jürgen A, Albrecht Urs (2016), REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor., in Journal of cell science
, 129(21), 4143-4154.
Hui Ka Yi, Ripperger Jürgen A (2015), Grab the wiggly tail: new insights into the dynamics of circadian clocks., in Nature structural & molecular biology
, 22(6), 435-6.
Fonseca Costa Sara S, Ripperger Jürgen A (2015), Impact of the circadian clock on the aging process., in Frontiers in neurology
, 6, 43-43.
Schnell Anna, Sandrelli Federica, Ranc Vaclav, Ripperger Jürgen A, Brai Emanuele, Alberi Lavinia, Rainer Gregor, Albrecht Urs (2015), Mice lacking circadian clock components display different mood-related behaviors and do not respond uniformly to chronic lithium treatment., in Chronobiology international
, 32(8), 1075-89.
Feillet Céline A, Bainier Claire, Mateo Maria, Blancas-Velázquez Aurea, Salaberry Nora L, Ripperger Jürgen A, Albrecht Urs, Mendoza Jorge (2015), Rev-erbα modulates the hypothalamic orexinergic system to influence pleasurable feeding behaviour in mice., in Addiction biology
, PMID: 2663.
Schmutz Isabelle, Chavan Rohit, Ripperger Jürgen A, Maywood Elizabeth S, Langwieser Nicole, Jurik Angela, Stauffer Anja, Delorme James E, Moosmang Sven, Hastings Michael H, Hofmann Franz, Albrecht Urs (2014), A specific role for the REV-ERBα-controlled L-Type Voltage-Gated Calcium Channel CaV1.2 in resetting the circadian clock in the late night., in Journal of biological rhythms
, 29(4), 288-98.
Schnell Anna, Chappuis Sylvie, Schmutz Isabelle, Brai Emanuele, Ripperger Jürgen A, Schaad Olivier, Welzl Hans, Descombes Patrick, Alberi Lavinia, Albrecht Urs (2014), The nuclear receptor REV-ERBα regulates Fabp7 and modulates adult hippocampal neurogenesis., in PloS one
, 9(6), 99883-99883.
Kowalska Elzbieta, Ripperger Juergen A., Hoegger Dominik C., Bruegger Pascal, Buch Thorsten, Birchler Thomas, Mueller Anke, Albrecht Urs, Contaldo Claudio, Brown Steven A. (2013), NONO couples the circadian clock to the cell cycle, in PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
, 110(5), 1592-1599.
Zani Fabio, Breasson Ludovic, Becattini Barbara, Vukolic Ana, Montani Jean-Pierre, Albrecht Urs, Provenzani Alessandro, Ripperger Juergen A, Solinas Giovanni (2013), PER2 promotes glucose storage to liver glycogen during feeding and acute fasting by inducing Gys2 PTG and G L expression., in Molecular metabolism
, 2(3), 292-305.
Chappuis Sylvie, Ripperger Jürgen Alexander, Schnell Anna, Rando Gianpaolo, Jud Corinne, Wahli Walter, Albrecht Urs (2013), Role of the circadian clock gene Per2 in adaptation to cold temperature., in Molecular metabolism
, 2(3), 184-93.
Jeyaraj Darwin, Haldar Saptarsi M, Wan Xiaoping, McCauley Mark D, Ripperger Jürgen A, Hu Kun, Lu Yuan, Eapen Betty L, Sharma Nikunj, Ficker Eckhard, Cutler Michael J, Gulick James, Sanbe Atsushi, Robbins Jeffrey, Demolombe Sophie, Kondratov Roman V, Shea Steven A, Albrecht Urs, Wehrens Xander H T, Rosenbaum David S, Jain Mukesh K (2012), Circadian rhythms govern cardiac repolarization and arrhythmogenesis., in Nature
, 483(7387), 96-9.
Kowalska Elzbieta, Ripperger Juergen A., Muheim Christine, Maier Bert, Kurihara Yasuyuki, Fox Archa H., Kramer Achim, Brown Steven A. (2012), Distinct Roles of DBHS Family Members in the Circadian Transcriptional Feedback Loop, in MOLECULAR AND CELLULAR BIOLOGY
, 32(22), 4585-4594.
Jeyaraj Darwin, Scheer Frank A J L, Ripperger Jürgen A, Haldar Saptarsi M, Lu Yuan, Prosdocimo Domenick A, Eapen Sam J, Eapen Betty L, Cui Yingjie, Mahabeleshwar Ganapathi H, Lee Hyoung-gon, Smith Mark A, Casadesus Gemma, Mintz Eric M, Sun Haipeng, Wang Yibin, Ramsey Kathryn M, Bass Joseph, Shea Steven A, Albrecht Urs, Jain Mukesh K (2012), Klf15 orchestrates circadian nitrogen homeostasis., in Cell metabolism
, 15(3), 311-23.
Ripperger Juergen A., Albrecht Urs (2012), REV-ERB-erating nuclear receptor functions in circadian metabolism and physiology, in CELL RESEARCH
, 22(9), 1319-1321.
Ripperger Jürgen A, Albrecht Urs (2012), The circadian clock component PERIOD2: from molecular to cerebral functions., in Progress in brain research
, 199, 233-45.
Schmutz I., Albrecht U., Ripperger J. A. (2012), The role of clock genes and rhythmicity in the liver, in MOLECULAR AND CELLULAR ENDOCRINOLOGY
, 349(1), 38-44.
Schmutz I, Albrecht U, Ripperger J A (2012), The role of clock genes and rhythmicity in the liver., in Molecular and cellular endocrinology
, 349(1), 38-44.
Ripperger Jürgen A, Merrow Martha (2011), Perfect timing: epigenetic regulation of the circadian clock., in FEBS letters
, 585(10), 1406-11.
Janich Peggy, Pascual Gloria, Merlos-Suárez Anna, Batlle Eduard, Ripperger Jürgen, Albrecht Urs, Cheng Hai-Ying M, Obrietan Karl, Di Croce Luciano, Benitah Salvador Aznar (2011), The circadian molecular clock creates epidermal stem cell heterogeneity., in Nature
, 480(7376), 209-14.
Ripperger Juergen A., Jud Corinne, Albrecht Urs (2011), The daily rhythm of mice, in FEBS LETTERS
, 585(10), 1384-1392.
Ripperger Jürgen A, Jud Corinne, Albrecht Urs (2011), The daily rhythm of mice., in FEBS letters
, 585(10), 1384-92.
2.1 SUMMARY: Adjustment of the mouse liver transcriptome to the photoperiod2.1.1 BACKGROUNDRhythmic transcription (circadian and/or food driven) is quite prominent in the liver. As a speculation, these rhythms synchronize the hepatic metabolism with the environment to enhance fitness. Although the liver is not directly light sensitive, the photoperiod (i.e. the day/night length ratio) affects the expression phase of hepatic circadian oscillator genes. Interestingly, two circadian genes have been identified in the liver, which in response to the photoperiod display different phase adjustments compared to the core oscillator components. In the case of these genes, special phase adjustment mechanisms may be important for the proper function of their gene products. However, it is unknown, how circadian genes, and all the other rhythmic genes in the liver, change their phase according to the photoperiod. Using biochemical and ultra-deep-sequencing approaches, we would like to understand I) the interplay between circadian oscillators and these adjustment processes; and II) the adjustment of the transcriptional networks to different photoperiods. We expect that our experiments will provide a comprehensive picture of the adjustment processes and the concomitant changes in the liver metabolism.2.1.2 WORKING HYPOTHESISSpecific transcriptional mechanisms adjust the hepatic transcriptome to the photoperiod.2.1.3 SPECIFIC AIMSI. Analysis of the relationship of circadian oscillators and adjustment mechanisms. We systematically analyze the circadian oscillator of knock-out mouse strains in different photoperiods. First, we measure their behavior and food uptake under these conditions. Secondly, we analyze the adjustment of their liver circadian oscillators to different photoperiods. This systematic analysis provides insights to understand the interplay between the circadian oscillator and the adjustment processes. To monitor the biological relevance of the adjustment processes, we will analyze the metabolic and detoxification potential of the liver using cytoplasm or isolated microsomes. In particular, we investigate glucose homeostasis and some detoxification pathways for anti-cancer drugs.II. Analysis of the mouse liver transcriptome in different photoperiods. We employ a global sequencing approach to analyze and compare the entire mouse liver transcriptome in different photoperiods. An adapted 5’-SAGE method allows identifying the peaks of rhythmic gene expression, the approximate position of their promoters, and outliers, whose phase adjustment deviates from the other genes. Specific transcription factors involved in adjustment or uncoupling processes emerge by motif scans. The importance of an identified transcriptional regulator to affect the phase of a group of target genes can then be verified in vitro by knock-down and over-expression experiments using hepatoma cells or primary hepatocytes and reporter genes driven by the identified promoters.2.1.4 SIGNIFICANCEOur experiments aim to get a coherent picture of the adjustment processes that occur in the liver transcriptome as a response to the changing photoperiod. Given that this organ is the major detoxification organ in mammals, it is necessary to understand these phase adjustments to optimally exploit the potential of e.g. chronotherapeutic treatments.