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J. Biol. Chem., Vol. 275, Issue 48, 37628-37637, December 1, 2000
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From the Drosophila C-terminal binding protein
(dCtBP) and Groucho have been identified as Hairy-interacting proteins
required for embryonic segmentation and Hairy-mediated transcriptional
repression. While both dCtBP and Groucho are required for proper Hairy
function, their properties are very different. As would be expected for a co-repressor, reduced Groucho activity enhances the hairy
mutant phenotype. In contrast, reduced dCtBP activity suppresses it. We
show here that dCtBP can function as either a co-activator or
co-repressor of transcription in a context-dependent
manner. The regions of dCtBP required for activation and repression are separable. We find that mSin3A-histone deacetylase complexes are altered in the presence of dCtBP and that dCtBP interferes with both
Groucho and Mad transcriptional repression. Similar to CtBP's role in
attenuating E1A's oncogenicity, we propose that dCtBP can interfere
with corepressor-histone deacetylase complexes, thereby attenuating
transcriptional repression. Hairy defines a new class of proteins that
requires both CtBP and Groucho co-factors for proper function.
Drosophila C-terminal Binding Protein
Functions as a Context-dependent Transcriptional
Co-factor and Interferes with Both Mad and Groucho Transcriptional
Repression*
§,,,§
Division of Basic Sciences and Program in
Developmental Biology, Fred Hutchinson Cancer Research Center, Seattle,
Washington 98109, the § Molecular and Cellular Biology
Program, University of Washington, Seattle, Washington 98195, and the
¶ Manitoba Institute of Cell Biology,
Winnipeg, Manitoba R3E 0V9, Canada
*
This work was supported by Medical Research Council of
Canada Grant MT 9186 (to J. R. D.), National Institutes of Health
(NIH) Grant 5T32 HD07183 (to T. M. P.), and NIH Grant GM47852 (to
S. M. P).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.
A Leukemia and Lymphoma Society Scholar. To whom
correspondence should be addressed: Division of Basic Sciences,
A1-162, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N.,
Seattle, WA 98109-1024. Tel.: 206-667-6466; Fax: 206-667-6497; E-mail: susanp@fred.fhcrc.org.
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