WDR-5 exhibits H3K4 methylation-independent activity, whereas RBBP-5 is essential for H3K4 methylation during embryonic development in C. elegans

Enrichment in the deposition of methyl groups at Histone 3 lysine 4 (H3K4) is associated with active transcription and bivalent chromatin. In yeast, there is evidence additionally supporting a role in repression during stress, In metazoans, H3K4 methylation levels are controlled by a conserved scaffold complex comprised of WDR5, ASH2L, and RBBP5 acting in association with one of the many H3K4 methyltransferases available. RBBP5 facilitates the assembly of the complex and association with the nucleosome. WDR5 coordinates the interaction between RBBP5 and the enzyme to facilitate methylation. WDR5 has moonlighting activities and is found in additional complexes, raising questions about WDR-5's specific role in H3K4 methylation. Using the C. elegans embryo system coupled with spike-in ChIP-seq and null alleles for wdr-5 and rbbp-5, we defined the impact that these two scaffolding components have on the deposition of H3K4 mono-, di-, and tri-methylation and on gene expression.