C. elegans
hcf-1 was found because of its similarity with human HCF-1. Human HCF-1 encodes a cellular component of a viral transcription activation complex required for herpes simplex virus (HSV) gene expression. A mutation in HCF-1 can arrest cell cycle progression in a mammalian cell line, but the mechanism of HCF-1 function in mammalian cells has not yet been elucidated. The product of C. elegans
hcf-1 (CeHCF) shares some known functional properties of HCF-1 including association with the HSV viral protein VP16. The goal of our research is to determine the cellular function of HCF proteins using C. elegans as a model organism. A chemically mutagenized C. elegans deletion library of R. Plasterk and colleagues (The Netherlands) was screened by PCR and an
hcf-1 deletion mutant was found. The isolated mutant has a 1465bp deletion which causes a frameshift in the
hcf-1 open reading frame. The absence of WT CeHCF protein in the homozygous deletion mutant was confirmed by western blot. These worms are viable and do not show any gross morphological or developmental defect. Analysis of the brood size at 15, 20, and 25C showed that the brood size of the mutant is about 50% of that of the WT at all three temperatures. At 15C, about 10% of mutant embryos also do not hatch. A further decrease of the temperature to 12C resulted in a further reduced mutant brood size (25% of WT) and only a 50% hatching rate. Thus, the
hcf-1 deletion mutant has a small brood size and a low temperature-sensitive embryonic arrest phenotype. This cold temperature-induced phenotype can be enhanced by propagating worms at low temperature (12C) for more than two generations. These results suggest a role for CeHCF in germ line and/or embryonic development.