Interaction and functional collaboration of p300 and C/EBPbeta.

Transcriptional coactivators such as p300 and CREB-binding protein (CBP) function as important elements in the transcription factor network, linking individual transactivators via protein-protein interactions to the basal transcriptional machinery. We have investigated whether p300 plays a role in transactivation mediated by C/EBPbeta, a conserved member of the C/EBP family. We ...
show that C/EBPbeta-dependent transactivation is strongly inhibited by adenovirus E1A but not by E1A mutants defective in p300 binding. Ectopic expression of p300 reverses the E1A-dependent inhibition and increases the transactivation potential of C/EBPbeta. Furthermore, we show that C/EBPbeta and p300 interact with each other and demonstrate that the sequences responsible for interaction map to the E1A binding region of p300 and the amino terminus of C/EBPbeta. Finally, we show that the minimal C/EBPbeta binding site of p300 acts as a dominant-negative inhibitor of C/EBPbeta. These observations identify p300 as a bona fide coactivator for C/EBPbeta. C/EBPbeta is highly expressed in the myelomonocytic lineage of the hematopoietic system and cooperates with Myb to activate mim-1, a gene specifically expressed during myelomonocytic differentiation. Recent evidence has shown that Myb recruits CBP (and presumably p300) as a coactivator and, in contrast to C/EBPbeta, interacts with the CREB binding site of p300-CBP. We show that p300 not only stimulates the activity of Myb and C/EBPbeta individually but also increases the synergy between them. Thus, our results reveal a novel function of p300: in addition to linking specific transcription factors to the basal transcriptional machinery, p300 also mediates the cooperation between transactivators interacting with different domains of p300.
Mesh Terms:
Acetyltransferases, Adenovirus E1A Proteins, Binding Sites, CCAAT-Enhancer-Binding Proteins, DNA-Binding Proteins, Genes, Reporter, Models, Genetic, Nuclear Proteins, Oncogene Proteins v-myb, Precipitin Tests, Protein Binding, Proteins, Repressor Proteins, Retroviridae Proteins, Oncogenic, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation
Mol. Cell. Biol.
Date: Nov. 01, 1997
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