Histone methylation is a key epigenetic modification that is central to the regulation of eukaryotic transcription. In the lower eukaryote, Saccharomyces cerevisiae (Baker’s yeast), it is controlled by a system of four methyltransferases (Set1p, Set2p, Set5p, and Dot1p) and four demethylases (Jhd1p, Jhd2p, Rph1p, and Gis1p). While the histone targets for these enzymes are well characterised, the connection of the enzymes with the intracellular signalling network and thus their regulation is poorly understood, in yeast and in all other eukaryotes. Here we report the detailed mass spectrometric characterisation of the eight S. cerevisiae enzymes, and show that they carry a total of 75 phosphorylation sites, 93 acetylation sites, and two ubiquitination sites. All enzymes are subject to phosphorylation, although demethylases Jhd1p and Jhd2p contained one and five sites respectively whereas other enzymes carried 14 to 36 sites. Enzymes with large numbers of sites are potential integrators of signalling data1. Phosphorylation was absent or under-represented on catalytic and other domains but strongly enriched for regions of disorder on methyltransferases, suggesting a role in the modulation of protein-protein interactions. We show that a phosphorylation cluster within an acidic and intrinsically disordered N-terminal region of methyltransferase Set2p regulates H3K36 methylation levels in vivo, thus supporting the functional relevance of disordered phosphosites. Strikingly, some phosphorylation events were evolutionarily conserved between yeast Set1p, Set2p, Rph1p, Gis1p, and their respective mammalian orthologs, and further sequences that contain phosphosites in yeast enzymes show relevant amino acid conservation in human. While most kinases upstream of the yeast histone methylation enzymes remain unknown, we model the possible connections between the signalling network and the histone-based gene regulatory system and propose an integrated regulatory structure. Our results provide a foundation for future, detailed exploration of the role of specific kinases and phosphosites in the regulation of histone methylation.