Light-driven circadian clock entrainment and DNA repair: Decoding transcriptional regulation by the D-box enhancer

• Applicant: Professor Dr. Nicholas S. Foulkes
• Subject Area: General Genetics and Functional Genome Biology ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431505125

The overall goal of this joint project involving the Foulkes (Germany) and Wang labs (China) is to identify the key transcription factor regulators of light induced gene expression in zebrafish.  We aim to understand how these light responsive transcription factors in turn contribute to resetting the circadian clock, controlling DNA repair systems as well as influencing other physiological systems. Furthermore, we wish to explore how these mechanisms adapt during evolution in response to long - term changes in lighting conditions. The Foulkes lab has shown that visible light and UV-regulated genes in zebrafish share a so-called D-box enhancer element in their control regions.  A family of 13 transcription factors binds to this element however it remains unclear why so many regulatory factors are involved. To tackle these issues, the Wang lab is generating a panel of genetically modified zebrafish lines where each of these D-box regulators is either inactivated or over-expressed in response to a heat shock. The Foulkes lab is establishing cell cultures from these lines which will be used for more detailed studies. In this project we will characterise in detail how the circadian clock and DNA repair respond to visible light and UV in these lines and cell cultures in order to pinpoint key D-box regulating factors which control these light-dependent systems. In addition we will take a broader approach by profiling light-driven changes in gene expression in selected lines in order to gain a global view of which genes are regulated by these key factors. Finally, we will examine the fate of these light-responsive, D-box binding factors in a blind cavefish which after 3 million years of isolation in constant darkness, lacks light induced gene expression and has circadian clock and DNA repair systems which do not respond to light.

• DFG Programme: Research Grants
• International Connection: China
• Partner Organisation: National Natural Science Foundation of China
• Cooperation Partner: Professor Han Wang, Ph.D.