The Drosophila Trithorax (TRX) protein plays a key role in maintaining active transcription of many master cell fate regulatory genes. Previously, TRX was thought to function mainly at the promoter by depositing the histone H3K4 trimethylation mark (H3K4me3) via its catalytic SET domain. However, recent findings have challenged this view, prompting new investigations into the function of TRX. Now, on p. 1129, Peter Harte, Feng Tie and colleagues reveal that TRX, along with TRX-related (TRR), is responsible for histone H3K4 monomethylation (H3K4me1), and not trimethylation, suggesting a role for TRX in stimulating enhancer-dependent transcription. In vivo studies support these findings, as a catalytically inactive form of TRX results in reduced H3K4me1, but no change in H3K4me3, in Drosophila embryos. The authors also show that TRX collaborates directly with CREB-binding protein (CBP) to promote robust H3K27 acetylation, which antagonises Polycomb silencing and may also stimulate enhancer-dependent transcription. These data provide exciting new insights into the mechanisms of epigenetic regulation in developing organisms.