Assembling a COMPASS.

Post-translational modifications of histone proteins lie at the heart of the epigenetic landscape in the cell's nucleus and the precise regulation of gene expression. A myriad of studies have showed that several histone-modifying enzymes are controlled by modulatory protein partner subunits and other post-transcriptional modifications deposited in the vicinity of the targeted site. All together, these mechanisms create an intricate network of interactions that regulate enzymatic activities and ultimately control the site-specific deposition of covalent modifications. In this Point-of-View, we discuss our evolving understanding on the assembly and architecture of histone H3 Lys-4 (H3K4) methyltransferase COMPASS complexes and the techniques that progressively allowed us to better define the molecular basis of complex formation and function. We further briefly discuss some of the challenges lying ahead and additional approaches required to understand mechanistic details for the function of such complexes.