Methylation of histones is central to chromatin regulation, and thus previously unknown mechanisms regulating genome function can be revealed through the discovery of new histone methyl marks. Here we identify Set5 as the first histone H4 methyltransferase, which monomethylates the critical H4 lysine residues 5, 8 and 12 in budding yeast. Set5's enzymatic activity functions together with the global chromatin-modifying complexes COMPASS and NuA4 to regulate cell growth and stress responses.
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