CFP-1 interacts with HDAC1/2 complexes in C. elegans development

CFP-1 (CXXC finger binding protein 1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in humans and C. elegans. This conserved epigenetic regulator is a 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. To further investigate the function of CFP-1, we have characterised C. elegans COMPASS mutants cfp-1(tm6369) and set-2(bn129). We 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 acts on a separate pathways to regulate fertility and development of C. elegans. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within COMPASS complex. We propose that CFP-1 could cooperate with COMPASS complex and/or HDAC1/2 in a context dependent manner.