Decoding transcriptional regulation in response to visible light in vertebrates

Sunlight influences various physiological processes, including circadian clock regulation and DNA repair via D-box enhancer elements. However, the broader transcriptional effects of visible light remain unclear. To investigate this, we compared light-mediated gene expression in zebrafish (Danio rerio) and the blind Somalian cavefish (Phreatichthys andruzzii), a species that evolved in perpetual darkness and lacks light-dependent circadian and DNA repair responses. We performed RNA sequencing of zebrafish and cavefish embryonic cell lines exposed to blue light (468 nm, for up to 6 hours), followed by gene ontology analysis and functional validation via bioinformatic, in vitro, and in vivo approaches. We revealed a light-dependent activation of a set of mitochondrial and heme metabolism genes via D-box enhancer elements. This transcriptional response was absent in cavefish cells. Further analysis revealed that while all zebrafish and cavefish PAR-bZip factors can activate the D-box, cavefish homologs exhibit diminished activity, suggesting an evolutionary reduction in light responsiveness. The D-box emerges as a key regulator of light-driven transcription in zebrafish, extending its role beyond circadian and DNA repair pathways to metabolic and mitochondrial processes. These findings provide insights into the evolution of light-sensing transcriptional mechanisms and lay the groundwork for future studies on their physiological implications. Overall design: RNA-seq pofiling of wild type zebrafish (D. rerio) embryonic cell line (PAC-2) and Somalian cavefish (P. andruzzii) embryonic cell line (EPA) exposed to 0h, 1h, 3h, 6h of blue light, 3 replicates each.