Klemz, Roman Reischl, Silke Wallach, Thomas Witte, Nicole Jürchott, Karsten Klemz, Sabrina Lang, Veronika Lorenzen, Stephan Knauer, Miriam Heidenreich, Steffi Xu, Min Ripperger, Jürgen A. Schupp, Michael Stanewsky, Ralf Kramer, Achim 2017-01-01 Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD+/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK– BMAL1 binding to target promoters. Pharmacological inhibition or genetic depletion of CO-producing heme oxygenases abrogates normal daily cycles in mammalian cells and Drosophila. In mouse hepatocytes, suppression of CO production leads to a global upregulation of CLOCK–BMAL1-dependent circadian gene expression and dysregulated glucose metabolism. Together, our findings show that CO metabolism is an important link between the basic circadian-clock machinery, metabolism and behavior. application/pdf https://folia.unifr.ch/global/documents/305297 https://folia.unifr.ch/documents/305297/files/rip_rrc.pdf https://folia.unifr.ch/documents/305297/files/rip_rrc_sm.pdf https://folia.unifr.ch/documents/305297/files/ric_rrc_sm2.txt eng info:eu-repo/semantics/altIdentifier/doi/10.1038/nsmb.3331 info:eu-repo/semantics/openAccess License undefined Nature Structural & Molecular Biology. - 2017, vol. 24, no. 1, p. 15-22 info:eu-repo/classification/udc/57 Reciprocal regulation of carbon monoxide metabolism and the circadian clock http://purl.org/coar/resource_type/c_6501