The novel function of CFP-1 in Caenorhabditis elegans development

CxxC finger protein 1 (Cfp1) is an evolutionally conserved CpG binding protein that binds to unmethylated CpG-rich promoters. This conserved epigenetic regulator is a part of the complex of proteins associated with Set1 (COMPASS) complex that contains Set1 in mammals and SET-2 in C. elegans as a histone 3 lysine 4 trimethylation (H3K4me3) methyltransferase. The canonical function of Cfp1 is to link the COMPASS complex to CpG island promoters to subsequently deposit H3K4me3 marks at the 5′ end of genes. Previous studies have indicated the importance of Cfp1 in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action of Cfp1 is well understood at the organismal level. To further investigate the conserved function of Cfp1, I used Caenorhabditis elegans cfp-1(tm6369) and set-2(bn129) mutants. I observed that deletion of cfp-1 or set-2 results in a drastic reduction of H3K4me3 levels and the stronger expression of heat shock and salt-inducible genes. That suggests H3K4me3 could play a repressive role in gene induction. Surprisingly, I found that despite both genes being essential for H3K4me3 deposition and gene induction, only loss of CFP-1 (but not SET-2) function can suppress an organogenesis defect caused by aberrant epidermal development. I next carried out the small genetic screen to identify the genes that can enhance or suppress CFP-1 function in the epidermal development. Results indicated that CFP-1 could interact genetically with Histone deacetylases (HDACs) to regulate epidermal development. To further investigate the genetic interaction between CFP-1 and HDACs, I conducted RNAi of HDACs on the cfp-1(tm6369) mutant and measured the effects on fertility. It was observed that CFP-1 but not SET-2 genetically interacts with HDAC1/2 complexes to promote fertility. In summary, this study suggests that apart from the function of CFP-1 in the H3K4me3 deposition, CFP-1 could interact with HDAC1/2 complexes in C. elegans development.