Journal Article
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. and Vallone, D.
Record Number:
5211
Year:
2018
Journal:
Scientific Reports
Volume:
8:13180
Abstract:
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.
Times Cited:
2