Polycomb complexes are major regulators of chromatin state. Variant Polycomb Repressive Complex 1 (PRC1) is responsible for histone H2A lysine 119 mono-ubiquitylation (H2AK119ub), a post-translational modification associated with the regulation of gene expression and development. Histone H2A ubiquitylation is believed to work cooperatively with PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) to repress gene expression, however recent evidence suggests that PRC1 may have H3K27me3-independent functions as well. In C. elegans, putative PRC1 component homologs,
mig-32 and
spat-3, and PRC2 homologs have different associated mutant phenotypes, suggesting they play partially distinct roles. However, whether C. elegans PRC1-like and PRC2 complexes and corresponding histone modifications function independently is currently unknown. To investigate the relationship between H2AK119ub and H3K27me3 in C. elegans, we performed ChIP-seq and RNA-seq profiling in wildtype and
mig-32 mutant embryos. We discovered that the majority of H2AK119ub and H3K27me3 peaks were distinct, with co-enrichment of the two histone modifications found at only a small subset of protein coding genes. Likewise, we observed a large decrease in H2AK119ub in
mig-32 mutants, whereas the distribution of H3K27me3 was not significantly affected, suggesting that H2AK119ub and H3K27me3 are regulated independently. Surprisingly, many H2AK119ub peaks were instead co-localized with H3K4me1 and H3K27ac, suggesting a role for H2AK119ub at enhancers. We found that H2AK119ub was also enriched at promoter regions of highly expressed genes and that H2AK119ub-associated genes were enriched for functional annotations related to nervous system development, which is consistent with roles for
mig-32 and
spat-3 in neuronal migration and axon guidance (Karakuzu et al. 2009 Development). We identified many genes with H2AK119ub-enriched promoters that were significantly upregulated in
mig-32 mutants. Interestingly, while many of these upregulated genes are highly expressed in wildtype worms, a subset are normally H3K27me3-repressed, implying a potential cooperation between H3K27me3 and H2AK119ub in regulation of a subset of genes. Together, our results indicate a dual role for H2AK119ub in the regulation of C. elegans gene expression, with both H3K27me3-dependent and H3K27me3-independent activities.