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A more recent version of this article appeared on July 14, 2000
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Papers In Press, published online ahead of print April 6, 2000
J. Biol. Chem, 10.1074/jbc.M001746200
Submitted on March 2, 2000
Accepted on April 5, 2000

A conserved transcription motif suggesting functional parallels between C. elegans SKN-1 and Cap'n'Collar-related bZIP proteins

Amy K Walker, Raymond See, Ceri Batchelder, Thip Kophengnavong, J. Timothy Gronniger, Yang Shi, and T. Keith Blackwell

Center for Blood Research, Harvard Medical School, Boston, MA 02115

Corresponding Author: blackwell{at}cbr.med.harvard.edu

In C. elegans, the predicted transcription factor SKN-1 is required for embryonic endodermal and mesodermal specification, and for maintaining differentiated intestinal cells postembryonically. The SKN-1 DNA binding region is related to the Cap'n'Collar (CNC) family of basic leucine zipper (bZIP) 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 likely significance in other CNC proteins. SKN-1 binds to and activates transcription through the p300/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 co-factors, and may have preserved some similar functions despite divergent DNA binding domains.


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