Trimethylation of histone H3K4, which marks active, transcribed genes, is catalyzed by the methyltransferase complex COMPASS and regulated in trans by prior ubiquitination of histone H2B Lys123 (H2BK123). The kinetochore protein Dam1, a component of the Dam1 (or DASH) complex that anchors kinetochores to microtubules, is the only other known substrate of COMPASS. Latham et al. now show that Dam1 dimethylation on K233 requires intact COMPASS and prior ubiquitination of H2BK123 in budding yeast, suggesting that histone modifications can direct modifications in non-histone proteins. Indeed, genetic deletion of the Rad6 E2 ubiquitin-conjugating enzyme responsible for H2BK123 ubiquitination or its corresponding E3 ligase Bre1 cause a phenotype associated with defective Dam1 methylation. By contrast, genetic deletion of the ubiquitin protease Ubp8 results in increased Dam1 dimethylation levels. The Paf1 transcription elongation complex, which is required for recruiting COMPASS and subsequent di- and trimethylation of H3K4 at gene promoters, is also required for Dam1 methylation. This raises the question of whether transcription plays a role in Dam1 methylation. Whereas H2BK123 ubiquitination and COMPASS recruitment to specific gene promoters require active RNA polymerase II (Pol II) transcription and the activity of Kin28 kinase (which phosphorylates the C-terminal domain of Pol II, marking the transition from transcription initiation to elongation), Dam1 methylation is independent of Kin28 activity. This suggests that Paf1 has functions independent of transcription in regulating kinetochore function, which leads to the question of how H3BK123 ubiquitination activity and the Paf complex are targeted to the centromere. It is possible that another kinase is required or that recruitment occurs through a Pol II–independent mechanism. Also, methylation of Dam1 occurs only in a functional kinetochore context, as mutations that disconnect the kinetochore from the centromere or the Dam1 complex from the rest of the kinetochore affect Dam1 methylation. The authors speculate that Dam1 methylation might be part of a phospho-methyl switch regulating kinetochore function and chromosome segregation, whereby methylation of Dam1 inhibits phosphorylation of flanking serine residues by Ipl1 kinase. (Cell 146, 709–719, 2011)