CBP-1 is the C. elegans homolog of mammalian histone acetyltransferase p300/CBP. Our lab has shown recently that CBP-1 is essential for the differentiation of endoderm, mesoderm and hypodermal tissues. In the endoderm differentiation CBP appears to antagonize the repressive activity of histone deacetylases, suggesting that the acetyltransferase activity of CBP plays an important role in endodermal gene activation. Studies in Drosophila and mammals have shown that, besides histones, p300/CBP also regulate the activities of a number of transcription factors through acetylation. These targets of p300/CBP include a Drosophila HMG-containing protein TCF that is related to the C. elegans POP-1protein. During C. elegans early embryogenesis, POP-1 plays an essential role in anterior-posterior cell fate decisions in C. elegans embryogenesis. Lack of POP-1 results in a mesodermal founder cell to adopt endodermal cell fate, suggesting that POP-1 functions to suppress genes important for endodermal fate in the mesodermal founder cell. To investigate the functional relationship between POP-1 and p300/CBP, we wish to determine whether p300/CBP can acetylate POP-1 in vitro and to analyze the consequence of POP-1 acetylation in C. elegans development. We have been able to show that p300 acetylates POP-1 efficiently in vitro and have identified the main lysine residue in POP-1 that is acetylated by p300. We have generated polyclonal antisera specific for this acetylation site and the results of these studies will be discussed. To investigate the molecular mechanisms that underlie the developmental function of POP-1, we also analyzed the transcriptional activity of POP-1. Consistent with its biological activity, we show that POP-1 can repress transcription. We identify a strong transcriptional repression domain that is necessary and sufficient for POP-1 to mediate repression in a GAL-4 fusion protein-based assay. We find multiple sequence motifs within the repression domain that each on its own can mediate repression. Further dissection of one such motif reveals amino acids that are important for the repression activity. POP-1 also possesses an activation domain, similar to its vertebrate homologs that have been shown to both activate and repress transcription.