The highly conserved COMPASS-like complexes recognize/bind specifically modified histone tails and carry out enzymatic histone modifications (methylation and demethylation of lysine residues). The complexes perform many essential functions in epigenetic gene control, including histone reader, writer and eraser functions, allowing for either gene activation or repression. The complexes are essential, with mutations in the fly and mammalian components directly linked to signaling pathway and stem cell defects, developmental and neurological disorders as well as a multitude of cancers. The COMPASS-like complexes are enriched on active, primed and poised enhancers and gene promoters to monomethylate lysine 4 of histone 3 (H3K4me1), considered the hallmark of transcriptional enhancers throughout the genome. We determined the COMPASS-like complex patterns of chromatin binding at various developmental stages in Drosophila using ChIP-seq analyses and identified potential transcription factors including nuclear receptors that collaborate with the complex in enhancer regulation. Genetic interaction studies incorporating null mutant alleles and RNAi combined with RNA-seq and gene specific ChIP analyses were used to examine effects of losing the complex on gene regulation and epigenetic modification. Our analyses revealed that the EcR hormone receptor is pre-engaged on the chromatin prior to ligand binding and that this engagement requires the stabilization by the COMPASS-like complex. Upon stimulation with hormone, the epigenetic modifications change in a precise manner representative of activation then enhancer ‘closing’ or poising for a subsequent round of activation, representing a form of enhancer pioneering.