Inhibition of p300/CBP by early B-cell factor.

Early B-cell factor (EBF) is a DNA binding protein required for early B-cell development. It activates transcription of several B-cell-specific genes, including the lambda5 gene, which encodes a protein necessary for signaling by the pre-B-cell receptor. In an effort to understand the mechanism by which EBF activates transcription, we examined ...
its interaction with the coactivator protein p300/CBP. We found that two domains of EBF each bind the histone acetyltransferase (HAT)/CH3 domain of p300/CBP both in vitro and in vivo. Surprisingly, transcriptional activation by EBF was not sensitive to E1A, a potent p300/CBP inhibitor. In fact, overexpressed EBF mimicked E1A by severely repressing the activity of several other transcription factors, including E47, a protein that acts cooperatively with EBF to promote transcription of the lambda5 gene. This broad inhibitory profile correlated with EBF's ability to repress the HAT activity of p300/CBP in vivo and in vitro. However, such a repressed complex is not likely to form at the lambda5 promoter in vivo since (i) EBF could not bind p300/CBP and DNA simultaneously and (ii) the cooperativity imparted by E47 was sensitive to E1A. Our data reveal an intriguing inhibitory property of EBF-a property shared only by E1A, Twist, Pu.1, and the Hox family of homeodomain proteins-and suggest that E47 and EBF play distinct roles during lambda5 promoter activation.
Mesh Terms:
3T3 Cells, Acetyltransferases, Animals, B-Lymphocytes, Cell Line, DNA-Binding Proteins, E1A-Associated p300 Protein, Fibroblasts, Genes, Reporter, Histone Acetyltransferases, Mice, Nuclear Proteins, Plasma Cells, Protein Structure, Tertiary, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae Proteins, Signal Transduction, Trans-Activators, Transcriptional Activation
Mol. Cell. Biol.
Date: Jun. 01, 2003
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