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J. Biol. Chem., Vol. 275, Issue 29, 22166-22171, July 21, 2000
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From the 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.
A Conserved Transcription Motif Suggesting Functional Parallels
between Caenorhabditis elegans SKN-1 and
Cap`n'Collar-related Basic Leucine Zipper Proteins*
,,,,§¶
Center for Blood Research and the
§ Department of Pathology, Harvard Medical School,
Boston, Massachusetts 02115
*
This work was supported by National Institutes of Health
Grants GM50900 (to T. K. B.), GM58012 (to Y. S.), and DK09416 (to A. K. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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