ZFIN ID: ZDB-PUB-180906-3
Evolution shapes the responsiveness of the D-box enhancer element to light and reactive oxygen species in vertebrates
Pagano, C., Siauciunaite, R., Idda, M.L., Ruggiero, G., Ceinos, R.M., Pagano, M., Frigato, E., Bertolucci, C., Foulkes, N.S., Vallone, D.
Date: 2018
Source: Scientific Reports   8: 13180 (Journal)
Registered Authors: Foulkes, Nicholas-Simon, Pagano, Cristina, Vallone, Daniela
Keywords: none
MeSH Terms:
  • Animals
  • Cell Line
  • Cells, Cultured
  • Circadian Clocks*
  • Cryptochromes/genetics
  • Cryptochromes/metabolism
  • Cyprinidae/genetics
  • Cyprinidae/physiology*
  • Enhancer Elements, Genetic*
  • Eye Proteins/genetics
  • Eye Proteins/metabolism
  • Fish Proteins/genetics
  • Fish Proteins/metabolism
  • Gene Expression Regulation
  • Light
  • NADPH Oxidases/metabolism
  • Period Circadian Proteins/genetics
  • Period Circadian Proteins/metabolism
  • Reactive Oxygen Species/metabolism*
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 30181539 Full text @ Sci. Rep.
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. Thus, during evolution, alterations in ROS-responsive signal transduction pathways underlie fundamental changes in peripheral clock photoentrainment.