Mammalian
p300 and CBP are closely related transcriptional coactivators that possess histone acetyltransferase (HAT) activity and function as integrators of transcription and signaling events. Recently, we have shown that a C. elegans gene closely related to
p300/CBP,
cbp-1 , is required to specify multiple differentiation events during embryogenesis. In endoderm differentiation,
cbp-1 appears to promote differentiation by antagonizing the repressive activity of histone deacetylases, suggesting that a balance between histone acetyltransferase and deacetylase may be important for endodermal differentiation (1). To further investigate the mechanisms underlying the differentiation-promoting activities of CBP-1, we isolated a
cbp-1 deletion mutant using a PCR-based approach. Antibody staining shows that this deletion resulted in a
cbp-1 null allele. The majority of embryos homozygous for the
cbp-1 deletion die around the 2-fold stage, suggesting that maternally provided CBP-1 is sufficient for the initiation of most differentiation events. We have begun to rescue the
cbp-1 deletion mutant using a YAC that carries a wildtype
cbp-1 gene. Preliminary results suggest that both maternal and zygotic defects can be rescued. Dead embryos segregated from the rescued animals morphologically resemble the
cbp-1 (RNAi) embryos. A detailed analysis of these embryos as compared to the
cbp-1 (RNAi) embryos and embryos derived from the
cbp-1 deletion mutant will be presented. Work is in progress to use this YAC-based approach to determine the role of various functional domains of CBP-1 (i.e. the HAT domain of CBP-1) in differentiation. (1) Shi, Y. and Mello, C. (1998) A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis elegans , Genes Dev. 12 , 943-55. Martin Victor is supported by a postdoctoral fellowship from the DAAD, Germany.