A conserved transcription motif suggesting functional parallels between Caenorhabditis elegans SKN-1 and Cap'n'Collar-related basic leucine zipper proteins

In Caenorhabditis elegans, the predicted transcription factor SKN-1 is requ ired for embryonic endodermal and mesodermal specification and for maintain ing differentiated intestinal cells post-embryonically. The SKN-1 DNA-bindi ng region is related to the Cap'n'Collar (CNC) family of basic leucine zipp er proteins, but uniquely, SKN-1 binds DNA as a monomer. CNC proteins are a bsent in C, elegans, however; and their involvement in the endoderm and mes oderm suggests some functional parallels to SKN-1, Using a cell culture ass ay, we show that SKN-1 induces transcription and contains three potent acti vation domains. The functional core of one domain is a short motif, the DID LID element, which is highly conserved in a subgroup of vertebrate CNC prot eins. The DIDLID element is important for SKN-1-driven transcription, sugge sting a likely significance in other CNC proteins. SKN-1 binds to and activ ates transcription through the p300/cAMP-rrespossvv element-binding protein -binding protein (CBP) coactivator, supporting the genetic prediction that SKN-1 recruits the C, elegans p300/CBP ortholog, CBP-1, The DIDLID element appears to act independently of p300/CBP, however, suggesting a distinct co nserved target. The evolutionarily preservation of the DIDLID transcription al element supports the model that SKN-1 and some CNC proteins interact wit h analogous cofactors and may have preserved some similar functions despite having divergent DNA-binding domains.