Abstract
In a modern society where artificial light sources rich in blue light (BL) are pervasive, concerns about the potential health impacts of BL on humans are growing. The damage BL causes to the human retina is well established, but its effects on non-retinal cells and the underlying mechanisms remain unclear. This study investigates the effects of phototoxic levels of BL on gene expression in adult Drosophila. We exposed Drosophila with genetically ablated eyes to continuous BL around the clock and assessed transcriptomic changes in non-retinal head tissues using RNAseq at three time points: 6, 10, and 14 days. Transcriptomic data revealed significant number of differentially expressed genes (DEGs) related to ribosomal biogenesis and energy metabolism pathways, including G6P metabolic process, fatty acyl-CoA biosynthesis, and glycolysis/ gluconeogenesis, due to BL exposure. To identify potential transcription factors (TFs) that may be involved in the BL-induced changes in gene expression, we utilized database of motifs to search the promoters and genomic sequences including introns of genes identified as DEGs. We determined that promoters for upregulated DEGs contain a DNA motif that is predicted to be bound by a TF with homology to a plant TF which is activated by light, encoded by CoRest. Further, a significant number of DEGs contained DNA motifs that could be targeted by another TF encoded by Xrp1, whose expression is significantly upregulated in BL. To test functional involvement of Xrp1 in BL response, we induced its overexpression in Drosophila neurons and showed that this significantly increased fly survival under BL, while knock out of Xrp1 accelerated mortality of BL-exposed flies. This study implicates potential positive feedback loop between CoRest and Xrp1, which is supported by previously published ChIPseq data, in response to blue light exposure and provides novel insights into the molecular mechanisms involved in mitigating its adverse effects.
