Drosophila C-terminal binding protein functions as a context-dependent transcriptional co-factor and interferes with both Mad and Groucho transcriptional repression
Tm. Phippen et al., Drosophila C-terminal binding protein functions as a context-dependent transcriptional co-factor and interferes with both Mad and Groucho transcriptional repression, J BIOL CHEM, 275(48), 2000, pp. 37628-37637
Drosophila C-terminal binding protein (dCtBP) and Groucho have been identif
ied as Hairy-interacting proteins required for embryonic segmentation and H
airy-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 th
e hairy mutant phenotype, In contrast, reduced dCtBP activity suppresses it
. We show here that dCtBP can function as either a co-activator or co-repre
ssor of transcription in a context-dependent manner. The regions of dCtBP r
equired for activation and repression are separable. We find that mSin3A-hi
stone deacetylase complexes are altered in the presence of dCtBP and that d
CtBP interferes with both Groucho and Mad transcriptional repression. Simil
ar to CtBP's role in attenuating E1A's oncogenicity, we propose that dCtBP
can interfere with corepressor-histone deacetylase complexes, thereby atten
uating transcriptional repression. Hairy defines a new class of proteins th
at requires both CtBP and Groucho co-factors for proper function.