Cellular identity during metazoan development is maintained by epigenetic modifications of chromatin structure. The balance between repressive and activating chromatin is maintained by the dynamic activity of specific protein which mediate histone variant incorporation, histone modifications, nucleosome remodeling and DNA methylation. HP1 family proteins function in both silencing and activation of gene expression by directly modifying chromatin structure depending on the chromosomal context. In mammalian cells, recruitment of HP1 to specific promoters by co-repressor proteins including TIF1 and Rb has been shown to be associated with gene repression. The C. elegans HP1 proteins HPL-1 and HPL-2 are required for several aspects of post-embryonic development by regulating the expression of specific genes. To better understand how HP1 proteins may influence gene expression in a developmental context, we carried out a candidate RNAi screen to identify suppressors of
hpl-1 and
hpl-2 phenotypes. We identified C. elegans SET-2, the homologue of yeast and mammalian SET1, as an antagonist of HPL-1 and HPL-2 activity in growth and somatic gonad development. Yeast Set1 and its mammalian counterparts SET1/MLL are H3 lysine 4 (H3K4) histone methyltransferases associated with gene activation as part of large multisubunit complexes. We show that the nematode counterparts of SET1/MLL complex subunits, including the WDR5 orthologue WDR-1, also antagonize HPL function in post-embryonic development. However, not all hpl phenotypes are equally suppressed. Analysis of the mutant phenotypes associated with
wdr-1 and
set-2 deletion alleles are consistent with SET1/MLL complex subunits having both shared and unique functions in development. Furthermore, as observed in other species, we find that SET1/MLL complex homologues differentially affect global H3K4 methylation. Altogether, our results suggest that in C. elegans, HP1 and a SET1/MLL related complex may play antagonistic roles in the epigenetic regulation of specific developmental programs.