Evidence from oyster suggests an ancient role for Pdx in regulating insulin gene expression in animals

• Published in: Nature Communications
• Main Authors: Fei Xu, Ferdinand Marlétaz, Daria Gavriouchkina, Xiao Liu, Tatjana Sauka-Spengler, Guofan Zhang, Peter W. H. Holland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature portfolio 2021
• Subjects: Pacific; Pacific oyster
• Online Access: http://id.nii.ac.jp/1394/00002041/; https://oist.repo.nii.ac.jp/?action=repository_uri&item_id=2262; https://oist.repo.nii.ac.jp/?action=repository_action_common_download&item_id=2262&item_no=1&attribute_id=22&file_no=1

Hox and ParaHox genes encode transcription factors with similar expression patterns in divergent animals. The Pdx (Xlox) homeobox gene, for example, is expressed in a sharp spatial domain in the endodermal cell layer of the gut in chordates, echinoderms, annelids and molluscs. The significance of comparable gene expression patterns is unclear because it is not known if downstream transcriptional targets are also conserved. Here, we report evidence indicating that a classic transcriptional target of Pdx1 in vertebrates, the insulin gene, is a likely direct target of Pdx in Pacific oyster adults. We show that one insulin-related gene, cgILP, is co-expressed with cgPdx in oyster digestive tissue. Transcriptomic comparison suggests that this tissue plays a similar role to the vertebrate pancreas. Using ATAC-seq and ChIP, we identify an upstream regulatory element of the cgILP gene which shows binding interaction with cgPdx protein in oyster hepatopancreas and demonstrate, using a cell culture assay, that the oyster Pdx can act as a transcriptional activator through this site, possibly in synergy with NeuroD. These data argue that a classic homeodomain-target gene interaction dates back to the origin of Bilateria. In vertebrates insulin is a direct transcriptional target of Pdx: the same is true in Pacific oysters and the authors show insulin-related gene, cgILP, is co-expressed with cgPdx in oyster digestive tissue, showing this gene interaction dates back to the origin of Bilateria.