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

CXXC finger binding protein 1 (CFP-1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in mammals and Caenorhabditis 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 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. 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. elegansCOMPASS 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.

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