SKN-1-independent transcriptional activation of glutathione S-transferase 4 (GST-4) by EGF signaling

What is it about?

Transcriptional reporters are often used in biological research to quantify the levels of gene expression of certain target genes. Especially in transparent organisms (such as the nematode Caenorhabditis elegans) they are often used to quantify gene expression in a non-invasive manner. This is done by coupling gene expression to fluorescent proteins, which can be visualized under a microscope. The resulting gene expression information can give valuable insights into the mode of action of certain drugs or interventions that aim to improve health or lifespan. We looked into the activation of the transcriptional reporter gst-4::GFP (CL2166) in C. elegans, and show that it can be activated by the EOR-1 transcription factor which mediates the effects of the epidermal growth factor (EGF) pathway in the nematode. Further, we found that the lifespan-extending compound Royalactin [also known as apalbumin 1 or Major Royal Jelly Protein 1 (MRJP1)] activates gst-4, in an EOR-1 dependent manner.

Featured Image

Why is it important?

While some researches are aware that the GFP reporter signal (driven by the gst-4 promoter) is not exclusively driven by the SKN-1 transcription factor, this is often overlooked. Our findings caution researchers within the C. elegans community to always rely on sufficient experimental controls when assaying SKN-1 transcriptional activity with a gst-4p::gfp reporter, such as SKN-1 loss-of-function mutants and/or additional target genes next to gst-4.