Recent studies show that proteins involved in chromatin remodeling such as histone acetylases play essential roles in differentiation, and these proteins are conserved from yeast, C. elegans to human. The mammalian transcriptional cofactors
p300 and CBP are histone acetylases and their C. elegans homolog
cbp-1 has been to be a critical regulator of cell fate and differentiation (1). Other histone acetylases such as P/CAF and TAFII250 are also conserved in C. elegans , but their biological functions are unknown. The P/CAF complex is composed of more than 20 proteins including previously identified proteins, such as TBP Associating Factors (TAFs), as well as novel proteins of unknown function (2). We find that components of the P/CAF complex such as p/CAF, the TAFs and
p130, a protein related to UV damaged-induced protein (DDB1), are conserved in C. elegans . The high level of sequence similarity suggests that these proteins are likely to share similar biological activities. Thus, insight into the biology and mechanisms of action of the p/CAF complex in C. elegans will be directly relevant to our understanding of the functions of mammalian p/CAF in cell growth and differentiation. We examined the role of
p130 in C. elegans by RNAi and identified an essential function for
p130 in C. elegans early embryogenesis.
p130 (RNAi) embryos arrest between 200 and 250-cells stage, as opposed to
cbp-1 (RNAi) embryos which arrest with an increased cell number (~1000 cells). Morphological and immunological analyses suggest that these embryos lack endoderm, mesoderm and hypodermal differentiation. Cell lineage analysis shows that the intestinal founder cells (Ea and Ep) fail to gastrulate, indicating an early defect associated with the failure of the
p130 (RNAi) to undergo endoderm differentiation. We are currently investigating the molecular mechanisms that underlie the role of
p130 in C. elegans embryogenesis. 1. Shi, Y., and Mello, C.C. (1998). A CBP/p300 homolog specifies multiple differentiation pathways in C. elegans . Gen. Dev. 12, 943-955. 2. Ogryzko,V., et al. (1998). Histones-like TAFs within the PCAF histone Acethylase Complex. Cell. 94, 35-44.