CFP-1 (CXXC finger binding protein 1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in mammals and C. elegans. This conserved epigenetic regulator is part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET-2 in C. elegans. Previous studies have indicated the importance of
cfp-1 in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action of
cfp-1 is well understood at the organismal level. Here we have used
cfp-1(
tm6369) and
set-2(
bn129) C. elegans mutants to investigate the function of CFP-1 in gene induction and development. We have characterised C. elegans COMPASS mutants
cfp-1(
tm6369) and
set-2(
bn129) and found that both
cfp-1 and
set-2 play an important role in the regulation of fertility and development of the organism. Furthermore, we found that both
cfp-1 and
set-2 are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt-inducible genes. Interestingly, we found that
cfp-1 but not
set-2 genetically interacts with Histone Deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP-1 outside of the COMPASS complex. Additionally, we found that
cfp-1 and
set-2 independently regulate fertility and development of the organism. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within the COMPASS complex. We propose that CFP-1 could cooperate with the COMPASS complex and/or HDAC1/2 in a context-dependent manner. This article is protected by copyright. All rights reserved.