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.