Abstract
In Caenorhabditis elegans, the predicted transcription factor SKN-1 is required for embryonic endodermal and mesodermal specification and for maintaining differentiated intestinal cells post-embryonically. The SKN-1 DNA-binding region is related to the Cap'n'Collar (CNC) family of basic leucine zipper proteins, but uniquely, SKN-1 binds DNA as a monomer. CNC proteins are absent in C. elegans, however; and their involvement in the endoderm and mesoderm suggests some functional parallels to SKN-1. Using a cell culture assay, we show that SKN-1 induces transcription and contains three potent activation domains. The functional core of one domain is a short motif, the DIDLID element, which is highly conserved in a subgroup of vertebrate CNC proteins. The DIDLID element is important for SKN-1-driven transcription, suggesting a likely significance in other CNC proteins. SKN-1 binds to and activates transcription through the p300/cAMP-responsive 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 conserved target. The evolutionarily preservation of the DIDLID transcriptional element supports the model that SKN-1 and some CNC proteins interact with analogous cofactors and may have preserved some similar functions despite having divergent DNA-binding domains.
Highlights
During development, establishment of cell fates frequently involves conserved regulatory pathways
Genetic evidence suggests that SKN-1 may interact functionally with cAMP-responsive elementbinding protein-binding protein (CBP)-1, the C. elegans ortholog of the p300/CBP transcription coactivators. (20). p300/CBP proteins are metazoan histone acetyltransferases that are involved in developmental and inducible gene expression and that are recruited by numerous activators (21), including the CNC protein p45NF-E2 (22)
The functional core of one domain consists of a short sequence (Fig. 1B) that is specific to SKN-1-related proteins and to the NRF group of CNC proteins
Summary
Establishment of cell fates frequently involves conserved regulatory pathways. The functional core of one domain consists of a short sequence (the DIDLID element) (Fig. 1B) that is specific to SKN-1-related proteins and to the NRF group of CNC proteins. A Short Transactivation Motif Specific to SKN-1 and Some CNC-related Basic Leucine Zipper Proteins—When expressed by transfection in human (HeLa) cells, SKN-1 strongly activated a reporter containing four SKN-1-binding sites (SKN-1/ TK-CAT) (Fig. 2), but not the corresponding control reporter lacking those sites (data not shown).
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