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 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.
Walker
A K
AK
Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
See
R
R
Batchelder
C
C
Kophengnavong
T
T
Gronniger
J T
JT
Shi
Y
Y
Blackwell
T K
TK
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D015801:Helminth Proteins / Q000235:genetics*; D016350:Leucine Zippers / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D015801:Helminth Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C116463:cnc protein, Drosophila; C073702:skn-1 protein, C elegans