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Evolution shapes the responsiveness of the D-box enhancer element to light and reactive oxygen species in vertebrates

Pagano, Cristina 1; Siauciunaite, Rima 1; Idda, Maria L. 1; Ruggiero, Gennaro 1; Ceinos, Rosa M. 1; Pagano, Martina 1; Frigato, Elena; Bertolucci, Cristiano; Foulkes, Nicholas S. 1; Vallone, Daniela 1
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)


The circadian clock is a highly conserved cell-autonomous mechanism that directs daily rhythms in most aspects of biology. Daily entrainment by environmental signals, notably light, is essential for its function. However, our understanding of the mechanisms and the evolution of photic entrainment remains incomplete. Fish represent attractive models for exploring how light regulates the circadian clock due to the direct light sensitivity of their peripheral clocks. Central to this property is the light induced expression of clock genes that is mediated by D-box enhancer elements. Here, using zebrafish cells, we reveal that the light responsive D-box enhancer serves as a nuclear target for reactive oxygen species (ROS). We demonstrate that exposure to short wavelengths of visible light triggers increases in ROS levels via NADPH oxidase activity. Elevated ROS activates the JNK and p38 MAP kinases and in turn, induces clock gene expression via the D-box. In blind cavefish and mammals, where peripheral clocks are no longer entrained by direct illumination, ROS levels are still increased upon light exposure. However, in these species ROS no longer induces D-box driven clock gene transcription. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000085695
Veröffentlicht am 05.09.2018
DOI: 10.1038/s41598-018-31570-8
Zitationen: 24
Web of Science
Zitationen: 23
Zitationen: 30
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2018
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000085695
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Scientific reports
Verlag Nature Research
Band 8
Heft 1
Seiten Art.-Nr.:13180 /1-17
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 04.09.2018
Nachgewiesen in Web of Science
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